MX2008003147A - Prion-specific peptoid reagents - Google Patents

Abstract

The invention relates to peptoid reagents that interact preferentially with a pathogenic form of a conformational disease protein as compared to a nonpathogenic form of the conformational disease protein where the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region, and at least one peptoid region between the amino-terminal region and the carboxy-terminal region where the peptoid region comprises 3 to about 30 N-substituted glycines, and optionally one or more amino acids. The invention also relates to methods of using the peptoids in detecting and isolating prions, and in the treatment and prevention of prion-related diseases.

Description

SPECIFIC PEPTOID REAGENTS FIELD OF THE INVENTION The invention relates to peptoid reagents useful for detecting and isolating prions, and in the treatment and prevention of prion-related diseases. The invention also relates to complexes, compositions and kits comprising the peptoid reagents and processes for preparing them.

BACKGROUND OF THE INVENTION Prion protein (PrPc) is a 33-35 kD protein of uncertain function and, in humans, is transcribed by a gene in the short arm of chromosome 20. The protease-resistant core of 27-30 kD ( prion, scrapie protein or PrPSc) is the functional component, with several isoforms responsible for "prion diseases" which are conformational diseases by proteins. Protein-forming diseases originate from an aberrant conformation transition of a protein (a conformation disease protein such as PrPc), which in turn leads to the self-association of the aberrant protein forms (eg. example, PrPSc) resulting in tissue deposition and damage. The prions (PrPSc) have a sheet conformation substantially REF. : 190442 folded more than the a-helical structure of normal PrPc, lack detectable nucleic acid, and generally do not develop an immune response. In general, protein conformation diseases share striking similarities in clinical presentations, typically a rapid progression from diagnosis to death after variable incubation lengths. In humans, prion diseases, also known as "transmissible spongiform encephalopathies" (TSEs), include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), Fatal familial insomnia and Kuru (see, for example , Isselbacher et al., Eds. (1994) Harrison's Principies of Internal Medicine, New York: McGraw-Hill, Inc., Medori et al. (1992) N. Engl. J. Med. 326: 444-9 ). In animals, TSEs include sheep scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy and chronic wasting disease of captive deer, mule and elk (Gajdusek, 1990) Subacute Spongiform Encephalopthies: Transmissible Cerebral Amyloidoses Caused by Unconventional Virases In: Virology, Fiedls, ed., New York: Raven Press, Ltd. (pp. 2289-2324)). Transmissible spongiform encephalopathies are characterized by the same markers: the presence of abnormal conformation (rich in beta, and resistant to proteinase K) of the prion protein that transmits the disease when experimentally inoculated in laboratory animals including primates, rodents and transgenic mice . Recently, the rapid dispersion of BSE and its correlation with an increased occurrence of TSEs in humans has led to an increased interest in the detection of TSEs in non-human mammals. The tragic consequences of an accidental transmission of these diseases (see, for example, Gajdusek, Infectious Amyloids and Prusser Prions In Fields Virology, Fields, et al., Eds. Philadelphia: Lippincott-Ravin, Pub. (1996); Brown et al. Lancet, 340: 24-27 (1992)), decontamination difficulties (Asher et al. (1986) In: Laboratory Safety: Principies and Practices, Miller ed., (Pp. 59-71) Am. Soc. Micro),, and concerns about BSE. { Bri tish Med-. J. (1995) 311: 1415-1421) underlie the urgency of having both a diagnostic test that can identify humans and animals with TSEs and therapies for infected subjects. Prions differ significantly from bacteria, viruses and viroids. The dominant hypothesis is that, unlike all other infectious pathogens, the infection is caused by an abnormal conformation of the prion protein, which acts as a template and converts normal prion conformations into abnormal and aberrant conformations. A prion protein was first characterized in the early 1980s (See, for example, Bolton, McKinley et al. (1982) Science 218: 1309-1311; Prusiner, Bolton et al. (1982) Biochemistry 21: 6942-6950; McKinley, Bolton et al. (1983) Cell 35: 57-62). Complete prion protein coding genes have since been cloned, sequenced and expressed in transgenic animals. (See, for example, Basler, Oesch et al. (1986) Cell 46: 417-428). The key feature of prion diseases is the formation of the abnormally configured protein (PrPSc) from the normal form of prion protein (cellular or non-pathogenic or PrPc). (See, for example, Zhang et al. (1997) Biochem. 36 (12): 3543-3553; Cohen & Prusiner (1998) Ann. Rev. Biochem. 67: 793-819; Pan et al. (1993) Proc. Na ti. Acad. Scí. USA 90: 10962-10966; Safar et al. (1993) J. Biol. Chem. 268: 20276-20284). The substantially ß-sheet structure of PrPSc compared to the non-diseased forms of PrPc folded a-helical has predominantly been revealed by optical spectroscopy and crystallography studies. (See, for example, Wille et al. (2001) Proc. Na t '1 Acad. Sci. USA 99: 3563-3568; Peretz et al. (1997) J. Mol. Biol. 2' 3: 614-622 Cohen &Prisiner, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, (pp: 191-228) Structural changes appear to be followed by alterations in biochemical properties: PrPc is soluble in non-denaturing detergents, PrPSc is insoluble, PrPc is easily digested by proteases, while PrPSc is partially resistant, resulting in the formation of an amino-terminally truncated fragment known as "PrPres" (Baldwin et al. (1995); Cohen &Prusiner (1995)). ), "PrP 27-30" (27-30 kDa) or "PK-resistant" form (resistant to proteinase K) In addition, PrPSc can convert PrPc to the pathogenic conformation See, for example, Kaneko et al. (1995) Proc. Na t 'l Acad. Sci. USA 92: 11160-11164; Caughey (2003) Br Med Bull. 66: 109-20. Detection of pathogenic isoforms of diseased proteins. The age of conformation in living subjects and samples obtained from living subjects has proved difficult. Thus, definitive diagnostic and palliative treatments for these transmissible and amyloid-containing conditions before the subject's death remain a challenge not yet substantially met. The histopathological examination of brain biopsies is risky for the subject and the lesions and amyloid deposits can be omitted depending on which part of the biopsy sample is taken. Likewise, there are still risks involved with biopsies in animals, patients and health care personnel. In addition, brain test results in animals are not normally obtained until the animal has entered the feed supply. Also, typically, antibodies generated against prion peptides recognize both PrPSc and denatured PrP but are unable to selectively recognize infectious (denatured) PrPSc. (See, for example, Matsunaga et al. (201) Proteins: Structure, Function and Genetics 44: 110-118). A number of tests for TSE are available (See, Soto, C. (2004) Nature Reviews Microbiol.2: 809, Biffiger et al. (2002) J. Virol.Meth.101: 79; Safar et al. (2002) Nature Biotech. 20: 1147, Schaller et al., Neuropathol Acta. (1999) 98: 437, Lañe et al. (2003) Clin. Chem. 49: 1774). However, all of these use brain tissue samples and are suitable only as post-mortem tests. Most of these require proteinase K treatment of the samples as well, which can be time consuming, incomplete digestion of PrPc can lead to false positive results and digestion of PK-sensitive PrPSc can produce false negative results. Thus, there remains a need for compositions and methods for detecting the presence of pathogenic prion proteins in various samples, for example in samples obtained from live subjects, in blood sources, in farm animals and in other human food supplies, and animals. There is still a need for methods and compositions for diagnosing and treating prion-related diseases. The invention is directed to these, as well as to other, important purposes.

Brief description of the invention The present invention relates to peptoid reagents that interact with a conformation disease protein such as a prion protein, preferably with a pathogenic form as compared to a non-pathogenic form of the conformation disease protein, which has the formula: where: each Q is independently an amino acid or an N-substituted glycine, and - (Q) n- defines peptoid region; Xa is H, (C? -C6) alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, acyl (C? -C6), aminoacyl (Ci-e), an amino acid, an amino protecting group or a polypeptide of 2 to about 100 amino acids, wherein Xa is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety; Xb is H, (Ci-Cd) alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (C? -C6) alkoxy, aryloxy, aralkoxy, a carboxy protecting group, an amino acid or a polypeptide of 2 to about 100 amino acids, wherein Xb is optionally substituted by a conjugated moiety that optionally binds through a linker portion; and n is 3 to about 30; wherein at least about 50% of the peptoid region - (Q) n_ comprises N-substituted glycines. The present invention also relates to peptoid reagents that are polyionic and have a net charge at a physiologically relevant pH. In some embodiments, the peptoid reagents have a net positive charge at a physiologically relevant pH, such as a charge of at least 3+ or at least 4+. The net charge can originate from one or more N-substituted glycines of the peptoid region. The present invention further relates to a peptoid reagent which preferably interacts with a pathogenic form of a conformation disease protein as compared to a non-pathogenic form of the conformation disease protein, wherein the reagent comprises an amino-acid region. terminal, a carboxy-terminal region and at least one peptoid region between the amino-terminal region and the carboxy-terminal region, wherein the peptoid region comprises 3 to about 30 N-substituted glycines and optionally one or more amino acids. The present invention further provides a peptoid reagent that preferably interacts with a pathogenic form of a conformation disease protein as compared to a non-pathogenic form of the conformation disease protein, wherein the reagent comprises a peptoid region containing 3 to 15 contiguous N-substituted glycines, and wherein the peptoid region has a net charge at physiologically relevant pH. In some embodiments, the net charge is a net positive charge such as a net charge of at least 3+ or at least 4+ at a physiologically relevant pH. In some embodiments, the peptoid reagent has a net charge of 2+ to 6+, 3+ to 5+, or 4+ at physiologically relevant pH. The peptoid reagents of the invention can be used in a wide range of applications, including as tools for isolating pathogenic prions or for detecting pathogenic prions in a sample, as components of a therapeutic or prophylactic composition and / or for generating prion-specific antibodies. For example, peptoid reagents that preferably interact with PrPSc compared to PrPc are useful for the direct detection of pathogenic forms obtained from living or sometimes live subjects, for example, diagnosis of a disease or to screen donated or donated blood samples. sift organs for organ donation. The peptoid reagents of the invention can be used to bind specifically to any PrPSc in the sample by forming a complex. The complex can be detected directly by methods such as UV / Visible spectroscopy, FTIR, nuclear magnetic resonance spectroscopy, Raman spectroscopy, mass spectroscopy, HPLC, capillary electrophoresis, surface plasmon resonance spectroscopy, Micro-Electro-Mechanical Systems (MEMS ), or can be detected by the binding of additional prion-specific reagents (eg, a second peptoid reagent or a prion-binding reagent (as defined herein)), to the PrPSc in the complex or after dissociation of the complex. Thus, the present invention relates to a method for the detection of the presence of a pathogenic prion in a sample, which comprises contacting the sample with a peptoid reagent of the invention under conditions that allow the binding of the peptoid reagent to the pathogenic prion, if present, to form a complex, and detect the formation of the complex, the formation of the complex being an indicator of the presence of the pathogenic prion. The method of detecting pathogenic prions in a sample also comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, in contact the first complex with the second peptoid reagent of the invention, optionally marked in detectable form, under conditions that allow the union of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of a second complex , the formation of the second complex being indicative of the presence of the pathogenic prion. In a further embodiment, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, removing any unbound sample. , contacting the first complex with a peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex , the formation of the second complex being indicative of the presence of the pathogenic prion. The first peptoid reagent optionally comprises a solid support that aids separation of the first complex from the unbound sample. In addition, the detection method of the invention may comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, removing the unbound sample, dissociating the pathogenic prion from the first complex in this manner by providing a dissociated pathogenic prion, contacting the dissociated pathogenic prion with a second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow attachment of the second peptoid reagent to the dissociated pathogen prion to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. The method of detecting pathogenic prion in a sample may also comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, contacting the first complex with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex and detect the formation of the second complex , the formation of the second complex being indicative of the presence of the pathogenic prion. In a further embodiment, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, removing any unbound sample. , contacting the first complex with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. The first peptoid reagent optionally comprises a solid support that aids separation of the first complex from the unbound sample. further, the detection method of the invention may comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, withdraw non-sample. bound, dissociating the pathogenic prion from the first complex thereby providing a dissociated pathogenic prion, contacting the dissociated pathogenic prion with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the binding reagent to prions to the dissociated pathogenic prion to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. In a further embodiment, the detection method of the invention may comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex. , removing unbound sample, dissociating the pathogenic prion from the first complex thus providing a first dissociated pathogen, contacting the dissociated pathogenic prion with a prion binding reagent under conditions that allow the binding of the prion binding reagent to the dissociated pathogenic prion to form a second complex and detect the formation of the second complex using a second prion binding reagent, optionally labeled in detectable form, the formation of the second complex being indicative of the presence of the pathogenic prion. Moreover, the detection method may comprise contacting the sample with a prion binding reagent under conditions that allow the binding of the prion binding reagent to the pathogenic prion, if present, to form a complex, remove unbound sample. , contacting the complex with a first peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. The prion binding reagent is optionally provided on a solid support. Moreover, the detection method may comprise providing a solid support comprising a peptoid reagent of the invention, combining the solid support with a labeled ligand in detectable form, under conditions that allow the binding of the labeled ligand in detectable form to the peptoid reagent, wherein the peptoid reagent of the support has a weaker binding affinity for the ligand than for the pathogenic prion, to form a first complex, combining the sample with the first complex under conditions that allow the binding of the pathogenic prion, if present in the sample, to the peptoid reagent of the first complex, thereby replacing the labeled ligand in detectable form in the first complex and forming a second complex comprising the peptoid reagent and the pathogenic prion, and detect the formation of the second complex, the formation of the second complex being an indicator of the presence of the pathogenic prion. The present invention further provides methods for detecting the presence of a pathogenic prion in a sample, comprising: contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a complex, remove the unbound sample from the complex, dissociate the pathogenic prion from the complex thus providing a dissociated pathogenic prion, contact the dissociated pathogenic prion with a second solid support under conditions that allow the dissociated pathogenic prion to adhere to the second solid support and detect the dissociated and adhered pathogenic prion using a prion binding reagent, optionally labeled in detectable form, wherein the binding of the prion binding reagent indicates the presence of the pathogenic prion. In some embodiments, dissociation is carried out by exposing the complex to high pH or low pH. In some embodiments, the method further comprises the step of neutralizing the pH. high or low pH after dissociation. In some embodiments, the dissociated pathogenic prion is denatured. The present invention further provides methods for detecting the presence of a pathogenic prion in a sample, comprising contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present , to form a first complex, remove the non-bound sample from the first complex, dissociate the pathogenic prion from the first complex thereby providing a dissociated pathogenic prion, contact the dissociated pathogenic prion with a second solid support, wherein the second solid support comprises a first anti-prion antibody, under conditions that allow the dissociated pathogen prion to bind to the first anti-prion antibody to form a second complex and detect the pathogenic prion dissociated from the second complex with a second anti-prion antibody, optionally labeled in detectable form , where the binding of the second anti-prion antibody indicates to the presence of the pathogenic prion. In some embodiments, dissociation is carried out by exposing the first complex at high pH or low pH. In some embodiments, the method further comprises the step of neutralizing the high pH or low pH after dissociation. In additional embodiments, the dissociated pathogenic prion is denatured. All of the above methods using prion binding reagents, the prion binding reagents can be, for example, anti-prion antibodies. The invention further provides methods for treating or preventing prion-related infections in animals. The invention is further directed to the detection or isolation of prions in a sample. The invention is further directed to providing a source of a sample substantially free of prions such as blood or food.

BRIEF DESCRIPTION OF THE FIGURES Figures 1A-1B show ELISA detection of PrPc in human plasma samples. Figure A shows ELISA measurements (RLU) for increasingly high amounts of plasma. Figure IB shows a standard curve for ELISA measurements (RLU) using known amounts of recombinant PrP protein. Figure 2 illustrates the amino acid sequence of human prion proteins (SEQ ID N0: 1) and mouse (SEQ ID N0: 2). Figure 3 illustrates an alignment of human prion proteins (SEQ ID NO: 3), Syrian hamster (hamster) (SEQ ID NO: 4), bovine (SEQ ID NO: 5), sheep (SEQ ID NO: 6), mouse (SEQ ID NO: 7), moose (SEQ ID NO: 8), deer fallow deer (fallow deer) (SEQ ID NO: 9), mule deer (mule) (SEQ ID NO: 10) and white tail deer (white) ( SEQ ID N0: 11). Elk, Deer, Mule and Deer White Tail only vary among themselves in two residues, S / N128 and Q / E226 (shown in bold). Figure 4 illustrates denaturing profiles of vCJD and sCJD.

DETAILED DESCRIPTION OF THE INVENTION Definitions The following selected terms will be described in the context used herein. Both the plural and singular forms of a term are included notwithstanding the form described. "Prion", "prion protein", "PrP protein" and "prp" are used interchangeably to refer to both the pathogenic prion protein form (also known as scrapie protein, pathogenic protein, pathogenic isoform, pathogenic prion and PrPSc) as well as the non-pathogenic prion form (also known as the form of cellular protein, cellular isoform, non-pathogenic isoform, non-pathogenic prion protein and PrPc), as well as the denatured form and several recombinant forms of the prion protein that may not have either the pathogenic conformation or the conformation. normal cell "Shaping disease protein" refers to the forms of pathogenic and non-pathogenic protein of a protein associated with a conformational disease wherein the structure of the protein has changed (e.g., has been misfolded or added), giving as resulting in an abnormal conformation such as unwanted fibril or amyloid polymerization in the context of a beta-folded sheet. Exemplary conformation disease proteins include, without limitation, prion proteins such as PrPSc and PrPc and variable domain amino acid variations of the immunoglobulin light chain (VL), the protein component of the antibody molecule, which are used with conformational diseases such as amyloidosis. A non-limiting list of diseases with associated proteins that assume two or more different conformations is shown below.

The use of the terms "prion", "prion protein", "PrP protein", "PrP" or "conformation disease protein" is not intended to be limited to polypeptides having the exact sequences to those described herein. It is readily apparent that the terms encompass conformation disease proteins of any of the identified or unidentified species (e.g., human, bovine) or diseases (e.g., Alzheimer's, Parkinson's, etc.). See also U.S. common property patent applications. Serial No. 10 / 917,646, filed August 13, 2004, U.S. Serial No. 11 / 056,950, filed on February 11, 2005 and international application PCT / US2004 / 026363, filed on August 13, 2004, all entitled "Specific Prion Peptide Reagents", which are incorporated herein by reference. way of reference in their totalities. One of ordinary skill in the art in view of the teachings of the present disclosure and technique may determine regions corresponding to the sequences described herein in any other prion proteins, using for example sequence comparison programs (e.g., Basic Local Alignment Search Tool (BLAST)) or identification and alignment of features or structural motives. "Pathogenic" means that the protein actually causes the disease, or that the protein is associated with the disease and therefore, is present when the disease is present. Thus, a pathogenic protein, as used herein, is not necessarily a protein that is the specific causative agent of any disease. Pathogenic forms of a protein may or may not be infectious. An example of a disease protein of pathogenic conformation is PrPSc. Accordingly, the term "non-pathogenic" describes a protein that does not normally cause disease or that is not normally associated with causing disease. An example of a disease protein of nonpathogenic conformation is PrPs. "Interacting" in reference to a peptoid reagent that interacts as a protein, eg, a protein fragment, means that the peptoid reagent binds specifically, not specifically or in some combination of specific and non-specific binding to the prion protein. It is said that a peptoid reagent "preferably interacts" with a pathogenic prion protein if it binds with greater affinity and / or greater specificity to the pathogenic form than non-pathogenic isoforms. A peptoid reagent that preferably interacts with a pathogenic prion protein is also known herein with a pathogenic prion-specific peptoid reagent. In some embodiments, the increased affinity and / or specificity is at least about 2 times, at least about 5 times, at least about 10 times, at least about 50 times, at least about 100 times, at least about 500 times, or at least approximately 1,000 times. It should be understood that a preferred interaction does not necessarily require interaction between a specific amino acid or residues and / or substitute amino acid motifs of each peptide. For example, in some embodiments, the peptoid reagents of the invention preferably interact with pathogenic isoforms, but, nevertheless, may be able to bind non-pathogenic isoforms at a weak but detectable level. For example, 10% less than the binding shown to the polypeptide of interest). Typically, a weak bond, or background bond, is readily discernible from the preferred interaction with the compound or polypeptide of interest, for example, by the use of suitable controls. In general, the peptoids of the invention bind to pathogenic prions in the presence of a 106-fold excess in non-pathogenic forms. "Affinity" or "binding affinity", in terms of the peptoid reagent that interacts as a conformation disease protein, refers to the binding strength and can be expressed quantitatively as a dissociation constant (Kd). The binding affinity can be determined using techniques well known to one of ordinary skill in the art. "Prion-related disease" refers to a disease caused wholly or in part by a pathogenic prion protein (e.g., PrPSc), for example, but not limited to, scrapie, bovine spongiform encephalopathies (BSE), mad cow disease, feline spongiform encephalopathies, Kuru, Creutzfeldt-Jakob disease (CJD), new variant Creutzfeldt-Jakob disease (nvCJD), chronic wasting disease (CD), Gerstmann-Strassler-Scheinker disease (GSS), and fatal familial insomnia (FFI) ). The term "denaturalized" or "denatured" has the conventional meaning applied to the structure of proteins and means that the protein has lost its native tertiary secondary structure. With respect to the pathogenic prion protein, a pathogenic prion protein "denatured" no longer retains the native pathogenic conformation and in this way the protein is no longer "pathogenic". The denatured pathogenic prion protein has a conformation similar or identical to that of the denatured non-pathogenic prion protein. However, for reasons of clarity herein, the term "denatured pathogenic prion protein" will be used to refer to the pathogenic prion protein that is captured by the peptoid reagent as the pathogenic isoform and subsequently denatured. "Physiologically relevant pH" refers to a pH of about 5.5 to about 8.5; or about 6.0 to about 8.0; or normally around 6.5 to about 7.5. "Aliphatic" refers to a straight or branched chain hydrocarbon portion. The aliphatic groups may include heteroatoms and carbonyl moieties. "Alkyl", whether used alone or as part of another group, refers to an aliphatic hydrocarbon chain and includes, but is not limited to, straight and branched chains containing the 6, 5, I to 4 or the 3 carbon atoms, unless explicitly specified otherwise. For example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, etc. they are encompassed by the term "alkyl". "Alkenyl" is intended to mean alkyl groups containing at least one double bond, for example, 2 to 7, 2 to 6, 2 to 5 or 2 to 4 carbon atoms, including, for example, but not limited to vinyl, allyl, 2-methyl-allyl, 4-but-3-enyl, 4-hex-5-enyl, 3-methyl-but -2-enyl and the like. "Alkynyl" is intended to indicate alkyl groups having at least one carbon-carbon triple bond, for example 2 to 7, 2 to 6, 2 to 5 or 2 to 4 carbon atoms. Exemplary alkynyl groups include ethynyl, propynyl, and the like. "Alkoxy", whether used alone or as part of another group, has its normal meaning of a group of the formula -O-alkyl, for example, methoxy, wherein alkyl is as defined herein. "Halo" or "halogen", when used alone or as part of another group, has its normal meaning of elements of group VII, for example, F, Cl, Br and I. "Aryl", when used alone or as part of another group, means an aromatic hydrocarbon system, for example, from 6 to 20, 6 to 14 or 6 to 10 ring carbon atoms, for example, 1, 2 or 3 rings, for example, phenyl, benzyl, naphthyl, naphthalene, anthracene, phenanthrenyl, anthracenyl, pine, and the like. Also included in the definition of aryl are aromatic systems containing one or more fused non-aromatic carbocyclyl or heterocyclyl rings, for example, 1, 2, 3, 4-tetrahydronaphthalene and indane. The aryl group containing a fused non-aromatic ring can be attached through an aromatic portion or the non-aromatic portion. "Aryl-alkyl" or "aralkyl" means a group of the formula -alkyl-aryl, wherein the aryl and alkyl have the definitions given herein. "Aryloxy" has its normal meaning of the group of the formula -O-aryl, for example, hydroxyphenyl, wherein the aryl is as defined herein. "Aralkoxy" has its normal meaning of the group of the formula -O-alkyl-aryl, for example, methoxyphenyl, wherein the alkoxy and the aryl are as defined herein. "Cycloalkyl", whether used alone or as part of another group, has its normal meaning of a cyclic alkyl, alkenyl or alkynyl group, for example, a saturated mono-, bi-, tri-cyclic hydrocarbon portion fused, bridged or spiro, for example, of 3-10 carbon atoms, for example, cyclopropyl. The term "cycloalkyl-aryl" is intended to mean a group of the formula -aryl-cycloalkyl wherein the aryl and cycloalkyl are as defined herein. "Cycloalkylalkyl" is intended to mean a group of the alkyl-cycloalkyl formula, for example, a cyclopropylmethyl or cyclohexylmethyl group, wherein the alkyl and cycloalkyl are as defined herein. As used herein, "heteroaryl" groups refer to an aromatic heterocycle having at least one heteroatom ring member such as sulfur, oxygen or nitrogen. Heteroaryl groups include monocyclic and polycyclic systems (e.g., having 2, 3 or 4 fused rings). Examples of heteroaryl groups include without limitation pyridyl, pyrimidinyl, pyrazyl, pyridazinyl, triazinyl, furyl (furanyl), quinolyl, isoquinolyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrryl, oxazolyl, benzofuryl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 1,2,4-thiadiazolyl, isothiazolyl, benzothienyl, purinyl, carbazolyl, benzimidazolyl, indolinyl and the like. In some embodiments, the heteroaryl group has from 1 to about 20 carbon atoms, and in additional embodiments from about 3 to about 20 carbon atoms. In some embodiments, the heteroaryl group contains 3 to about 14, 3 to about 7 or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to about 4, 1 to about 3 or 1 to 2 heteroatoms. As used herein, "heterocycloalkyl" refers to non-aromatic heterocycles that include cyclized alkyl, alkenyl and alkynyl groups wherein one or more of the ring-forming carbon atoms is replaced by a hetero atom such as an O atom., N or S. Exemplary "heterocycloalkyl" groups include morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, 2,3-dihydrobenzofuryl, 1,3-benzodioxole, benzo-1,4-dioxane, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl and the like. The definition of heterocycloalkyl also includes those portions having one or more fused aromatic rings (i.e., having a common bond with) to the non-aromatic heterocyclic ring, eg, phthalimidyl, naphthalimidyl and benzo derivatives of heterocycles such as indolene and isoindolene. In some embodiments, the heterocycloalkyl group has from 1 to about 20 carbon atoms, and in additional embodiments from about 3 to about 20 carbon atoms. In some embodiments, the heterocycloalkyl group contains 3 to about 14, 3 to about 7 or 5 to 6 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 1 to about 4, 1 to about 3 or 1 to 2 heteroatoms. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double or triple bonds. "Heteroarylalkyl" refers to a group of the formula -alkyl-heteroaryl, wherein alkyl and heteroaryl are as defined herein. "Acyl" refers to a group of the formula -C (O) -alkyl. In some embodiments, the acyl group has from 1 to 10, 1 to 8, I to 6 or 1 to 4 carbon atoms. "Aminoacyl" refers to a group of the formula -C (O) -alkylamino, wherein alkyl is as defined herein. "Alkylamino" refers to a group of the formula -NH-alkyl, wherein alkyl is as defined herein.

"Dialkylamino" refers to a group of the formula -N (alkyl) 2, wherein alkyl is as defined herein. "Haloalkyl" refers to an alkyl group substituted by one or more halogens, wherein alkyl and halogen are as defined above. "Alkoxyalkyl" refers to a group of the formula -alkyl-alkoxy, wherein alkyl and alkoxy are as defined herein. "Carboxyalkyl" refers to a group of the formula -alkyl-COOH, wherein alkyl is as defined herein. "Carbamyl" refers to a group of the formula -C (0) NH2. "Carbamylalkyl" refers to a group of the formula -alkyl-C (O) NH2, wherein alkyl is as defined herein. "Guanidinoalkyl" refers to a group of the formula -alkyl-NHC (= NH) NH2, wherein alkyl is as defined herein. "Thiol" refers to a group of the formula -SH. "Alkyltiol" refers to a group of the formula -S-alkyl, wherein alkyl is as defined herein. "Alkylthioalkyl" refers to a group of the formula -alkyl-S-alkyl, wherein alkyl is as defined herein. "Imidazolylalkyl" refers to a group of the formula -alkyl-imidazolyl, wherein alkyl is as defined herein. "Piperidylalkyl" refers to a group of the formula -alkyl-piperidinyl, wherein alkyl is as defined herein. "Naphthylalkyl" means a group of the formula -alkyl-naphthyl, for example, (8'-naphthyl) methyl, wherein naphthyl has its normal meaning and alkyl is as defined herein. "Indolylalkyl" means a group of the formula -alkyl-indole, "for example, 3'-indolylethyl and 3'-indolylmethyl, wherein the indole has its normal meaning and alkyl is as defined herein. "Heterocyclyl containing N" is intended to refer to any heteroaryl or heterocyclylalkyl group containing at least one ring-forming N atom. Heterocyclyl groups containing N examples include pyridinyl, imidazolyl, piperidinyl, piperazinyl, pyrrolyl, indolyl and the like. "Heterocyclylalkyl containing N" is intended to refer to alkyl substituted by heterocyclylalkyl containing N.

"Amino" and "primary amino" refer to NH2.

"Secondary amino" refers to NHR and "tertiary amino" refers to NR2, wherein R is any suitable substituent. "Ammonium" is intended to refer to the group -N (R) 3+ wherein R may be any suitable portion such as alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, etc. Amino acid "refers to any of the twenty-genetically encoded amino acids and naturally occurring or protected derivatives thereof. The protected derivatives of amino acids may contain one or more protecting groups on the amino portion, portion carboxy or side chain moiety. Examples of amino protecting groups include formyl, TRIFILO, phthalimido, trichloroacetyl, chloroacetyl, bromoacetyl, iodoacetyl groups and urethane-type blocking, such as benzyloxycarbonyl, 4-fenilbenciloxicarbonilo, 2-methylbenzyloxycarbonyl, 4-metoxibenciloicarbonilo, 4-fluorobenciloxicarbonilo, 4-chlorobenzyloxycarbonyl , 3-chlorobenzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 2, 4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cianobenciloxicarbonilo, t-butoxycarbonyl, 2- (4-Xenil) -isopropoxicarbonilo, 1,1_ difenileti- 1-Iloxycarbonyl, 1,1-diphenylprop-1-yloxycarbonyl, 2-phenylprop-2-yloxycarbonyl or 2- (p-toluyl) prop-2-yloxycarbonyl, ciclopentaniloxi-carbonyl, 1-metilciclopentaniloxicarbonilo, ciclohexaniloxicarbonilo, 1-metilciclohexaniloxicarbonilo, 2-metilciclohexaniloxicarbonilo, 2- (4-toluilsulfonil) ethoxycarbonyl, 2- (methylsulfonyl) ethoxycarbonyl, 2- (triphenylphosphino) -ethoxycarbonyl, fluorenylmethoxycarbonyl ("FMOC"), 2- (trimethylsilyl) ethoxycarbonyl, allyloxycarbonyl, 1- (trimethylsilylmethyl) proa-1-enyloxycarbonyl, 5-benzyloxylylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4- (decyloxy) benzyloxycarbonyl, isobornyloxycarbonyl, 1-piperidyloxycarbonyl and Similar; benzoylmethylsulfonyl group, 2-nitrophenylsulfonyl, diphenylphosphine oxide and similar amino protecting groups. Examples of carboxy protecting groups include methyl, p-nitrobenzyl, p-methylbenzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, 2,4-dimethoxybenzyl, 2,4,6-trimethoxybenzyl, 2,4,6-trimethylbenzyl, pentamethylbenzyl, 3,4-ethylenedioxybenzyl, benzhydryl, 4, '-dimethoxybenzhydryl, 2, 2', 4, 4 '-tetramethoxybenzhydryl, t-butyl, t-amyl, trifly, 4-methoxytrityl, 4,4'-dimethoxytrityl, '4,4', 4"-trimethoxytrityl, 2-phenylprop-2-yl, trimethylsilyl, t-butyldimethylsilyl, phenacyl, 2,2,2-trichloroethyl, beta- (di (n-butyl) methyl (silyl) ethyl, p-toluenesulfonylethyl, 4-nitrobenzylsulfonylethyl, allyl, cinnamyl, 1- (trimethylsilylmethyl) proa-l-en-3-yl and similar portions The species of protecting group employed is not critical as long as the derivative protecting group can be selectively removed at the appropriate point without altering the remainder of the molecule, Additional examples of protecting groups are found in E. Haslam, Protecting Groups in Organi c Chemistry, (JGW McOmie, ed., 1973) , in Chapter 2, and T. Greene and PGM Wuts, Protective Groups in Organic Synthesis, (1991), in Chapter 7, the descriptions of each of which are incorporated herein by way of reference in their totalities. "Peptoide" is generally used to refer to a peptide mimic containing at least one of p reference two or more, amino acid substitutes, preferably N-substituted glycines. The peptoids are described among others, in the patent of E.U.A. No. 5,811,387. "N-substituted glycine" refers to a residue of the formula - (NR-CH2-C0) - wherein each R is a non-hydrogen moiety such as those selected independently of (C2-Cd) alkyl, haloalkyl (C? -C6), (C2-C6) alkenyl, (C2-C6) alkynyl, (C6-C? 0) cycloalkylaryl, Ci-C? Aminoalkyl), (Ci-C?) Ammonioalkyl, hydroxyalkyl (Ci-Cß), (C?-C6) alkoxy-(C?-C6) alkyl, carboxy, carboxyalkyl (C2-C6), carbamylalkyl (C2-C6), guanidino, guanidinoalkyl (C ?-) C6), amidino, amidinoalkyl of (C? ~ C6), thiol, alkylthiol of (C? -C6), alkylthioalkyl of 2-10 carbon atoms, heterocyclyl containing N, heterocyclylalkyl of (C? -C6) containing N , imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms and arylalkyl of Cß), where each R portion is s optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (Ci-Cß) alkoxy. In some embodiments of - (NR-CH2-C0) -, R is (C2-C6) alkyl, (C? -C6) haloalkyl, (C2-C) alkenyl, (C2-C6) alkynyl, cycloalkyl -alkyl (Cß-Cio), aminoalkyl of (Ci-Cß), hydroxyalkyl of (Ci-Cß), alkoxy of (C? -C6) -alkyl of (C? -C6), carboxy, carboxyalkyl of (C2-) C6), carbamyl, carbamylalkyl of (C2-Ce), guanidino, guanidinoalkyl of (C? -C6), thiol, alkylthiol of (C? -C6), alkylthioalkyl of 2-10 carbon atoms, imidazolyl, imidazolylalkyl of 4- 10 carbon atoms, piperidinyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, din-phenylalkyl of (C1-C6) or arylalkyl of (Ci) -Ce); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (Ci-Ce) alkoxy.

In some embodiments of - (NR-CH2-C0) -, R is (C2-C2) alkyl, (C 1 -C 6) aminoalkyl, (C 1 -C 6) hydroxyalkyl, (C 6 -C 6) alkoxy alkyl (C? -C6), guanidinoalkyl of (C? -C6), indolyalkyl of 9-15 carbon atoms, naphthylalkyl of 11-16 carbon atoms, diphenylalkyl of (C? -C6) or arylalkyl of (C? -C6), substituted with 1-3 substituents independently selected from halogen, hydroxy or (C? -C6) alkoxy. In some embodiments of - (NR-CH2-CO) -, R is a portion that is charged at a physiologically relevant pH. Examples of R positively charged at physiologically relevant pH include, for example, aminoalkyl of (Ci-Ce), ammonioalkyl of (Ci-Cß), guanidino, guanidinoalkyl of (Ci-Cß), amidino, amidinoalkyl of (Ci-Cß), N-containing heterocyclyl and (C? -C6) heterocyclylalkyl containing N, wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, C 1 -C 3 methoxy and C 1 -C 3 alkyl. In some embodiments of - (NR-CH2-CO) -, R is a portion that is neutral at physiologically relevant pH. Examples of neutral R at physiologically relevant pH include, for example, (C2-C6) alkenyl, (Ci-Ce) haloalkyl, (C2-C6) alkenyl, (C2-Ce) alkynyl, cycloalkyl-aryl ( C6-C? 0), (C? -C6) alkoxy-(Ci-Ce) alkyl, 2-1-carbon atoms alkylthioalkyl, (C? -C6) diphenylalkyl, and (Ci-Ce) arylalkyl Additional examples include ethyl, prop-1-yl, prop-2-yl, 1-methylprop-1-yl, 2-methylprop-1-yl, 3-phenylpropi-1-yl, 3-methylbutyl, benzyl, 4-chloro-benzyl, 4-methoxy-benzyl, 4-methyl-benzyl, 2-methylthioet-1-yl and 2,2-diphenylethyl. In some embodiments of - (NR-CH2-CO) -, R is aminoalkyl of (Ci-Ce) (e.g., aminobutyl). Additional exemplary N-substituted glycines include those in which R is ethyl, prop-1-yl, prop-2-yl, methylprop-1-yl, 2-methylprop-1-yl, 3-phenylpropi-1-yl, 3-methylbutyl, benzyl, 4-hydroxybenzyl, 4-chloro-benzyl, 4-methoxy-benzyl, 4-methyl-benzyl, 2-hydroxyethyl, mercaptoethyl, 2-aminoethyl, 3-propionic acid, 3-aminopropyl, 4-aminobutyl , 2-methylthioet-1-yl, carboxymethyl, 2-carboxyethyl, carbamylmethyl, 2-carbamylethyl, 3-guanidinoprop-1-yl, imidazolylmethyl, 2,2-diphenylethyl or indole-3-yl-ethyl. Also included are salts, esters and protected forms (eg, N-protected with Fmoc or Boc, etc.) of the N-substituted glycines. Methods for making amino acid substitutes, including N-substituted glycines, are described, inter alia, in the US patent. No. 5,811,387, which is incorporated herein by reference in its entirety. "Monomer" or "subunit" refers to a molecule that can be linked to other monomers to form a chain, for example, a peptide. The N-substituted amino acids and glycines are exemplary monomers. When bound to other monomers, a monomer can be referred to as "waste." "Peptoid reagent" as used herein refers to a peptide-like polymer in which one or more residues comprises an N-substituted glycine, as described hereinafter, and which preferably interact with the pathogenic form of a conformation disease protein, particularly with a pathogenic prion protein. The linkage of each of the N-substituted glycines in a straight or branched chain optionally together with amino acids and / or other amino acid substitutes can produce "peptoid reagents", such as those described herein. The bonds typically constitute peptide bonds (ie, amides). "Peptide" refers to an amide compound comprising at least two amino acids joined by a peptide bond, ie, by the amino group bond of one amino acid to the carboxyl group of another amino acid. Peptide is used herein interchangeably with "oligopeptide" or "polypeptide" and no polymer of particular size is implied by the use of these terms. Non-limiting lengths of peptides suitable for use in the present invention include peptides of 3 to 5 residues long, 6 to 10 residues long (or any integer between them), 11 to 20 residues long (or any integer between them), 21 to 75 residues long (or any integer between them), 75 to 100 (or any whole between them), or polypeptides of more than 100 residues long. Typically, the peptides useful in this invention can have a maximum length suitable for the desired application. The peptide may have between about 2 and about 100, about 2 and about 50, about 2 and about 20, about 2 and about 10, about 2 and about 8 or about 2 and about 5 residues long. The "likeness" between an amino acid in a peptide and its amino acid substitute does not have to be exact. For example, one can replace lysine with an N-substituted glycine residue (e.g., - (NR-CH2-C0) -) in which R is an aminoalkyl group such as aminomethyl, 2-aminoethyl, 3-aminopropyl, -aminobutyl, 5-aminopentyl or 6-aminohexyl. Serine can be replaced with, for example, hydroxyalkyl groups such as hydroxymethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, and the like. In general, as an initial approach, a conventional amino acid can be replaced with an N-substituted glycine analog having a side chain of a similar character, for example, hydrophobic, hydrophilic, polar, non-polar, aromatic, etc. Further testing and optimization of the peptide substituted with amino acid can be carried out by the method described herein. A "conjugated portion" is a molecule covalently linked to the peptoid reagent. Exemplary conjugated moieties include effector molecules, substrates, markers, entanglement agents, binding agents, polymeric scaffolds, antigenic agents, separating molecules and the like. The binding of conjugated groups to peptides and analogs thereof is well documented in the prior art. The conjugated portion can be attached directly to the peptoid reagent or linked through a linker portion. In some of these embodiments, the conjugate reaction is linked to the peptoid reagent in the amino-terminal region of the carboxy-terminal region. In additional embodiments, the conjugated portion is bound in a terminal sub-unit such as an amino-terminal subunit or a carboxy-terminal subunit. In some embodiments, the conjugated portion is an entanglement agent or binding agent. In some embodiments, the conjugated portion comprises biotin or a mercapto group. In some embodiments, the conjugated portion comprises a detectable label. In some embodiments, the peptoid reagent comprises two or more conjugates. The terms "label", "label", "detectable label" and "label in detectable form" refer to a molecule capable of detection, including, but not limited to, radioactive isotopes, fluorescers, luminescers, chemiluminescers, enzymes, substrates of enzyme, enzymatic co-factors, enzyme inhibitors, chromophores, dyes, metal ions, metal sols, ligands (for example biotin or haptens), fluorescent nanoparticles, gold nanoparticles and the like. The term "fluorescer" refers to a substance or a portion thereof that is capable of exhibiting fluorescence on the detectable scale such as a fluorophore. Particular examples of labels that can be used with the invention include, but are not limited to fluorescein, rhodamine, dansyl, umbelliferone, Texas red, luminol, acridinium esters, NADPH, beta-galactosidase, horseradish peroxidase, glucose oxidase, alkaline phosphatase and urease. The label can also be an epitope marker (eg, His-His), an antibody or an amplifiable or otherwise detectable oligonucleotide. The term "effector compound" includes any compound that binds to a biological receptor site and effects a biochemical event after this binding. Thus, an effector compound includes a pharmaceutical drug as well as insecticides, but is not limited to any of them. The term "entanglement agent" refers to portions that have functionalities capable of forming covalent bonds with other molecules or polymeric scaffolds. Examples of entanglement agents include those having one or more mercapto, hydroxyl, amino and carboxyl terminal functionalities and similar functionalities. In some embodiments, the entanglement agent has at least one mercapto functionality. The term "binding agent" refers to a portion that is capable of binding, through non-covalent interactions, with another molecule or substance such as a polymeric scaffold. An exemplary binding agent is biotin or derivative thereof. A "linker portion", "link portion" or "linker" refers to a portion that binds the conjugated portion to the peptoid reagent. In some embodiments, the linker portion is a group that has at least one link region with the formula -. { NH (CH2) mC (O)} p- wherein m is 1 to 10 and p is 1 to 5. In some embodiments, the linker portion comprises at least one residue of aminohexanoic acid (Ahx) or fragment thereof. These portions may further increase the interaction of the peptoid reagent with the prion proteins and / or further increase the detection of the prion proteins.

Peptoid Reagents The present invention provides peptoid reagents that interact with conformation disease proteins such as prion proteins, complexes, compositions and kits containing the peptoid reagents and methods for use in the detection and isolation of conformation disease proteins such as PrPSc. The peptoid reagents of the invention can be used in the treatment and prevention of protein-forming diseases, for example, prion diseases such as TSEs, as well as in a method for providing a food source or blood that is substantially free of pathogenic prions. The invention provides a peptoid reagent that preferably interacts with a pathogenic form of a conformation disease protein compared to another non-pathogenic form of the conformation disease protein having a formula of: Xa- (Q) n-Xb in where: each Q is independently an amino acid or an N-substituted glycine and - (Q) n_ defines a peptoid region; Xa is H, (C? -C6) alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, acyl (Ci-Ce), aminoacyl (Ci-C?), An amino acid, an amino protecting group or an polypeptide of 2 to about 100 amino acids, wherein Xa is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety. Xb is H, (Ci-Ce) alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (C? -C6) alkoxy, aryloxy, aralkoxy, a carboxy protective group, an amino acid or a polypeptide of 2 to about 100 amino acids, wherein Xb is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety and n is 3 to about 30 (ie n is 3, 4, 5, 6, 7 , 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 or more); wherein at least about 50% of the peptoid region - (Q) n- comprises N-substituted glycines. In some embodiments, each Q is independently an N-substituted glycine. In some embodiments, the peptoid reagent has a formula of Xa-. { Q) n-Xh, wherein n is about 4 to about 30, preferably about 5 to about 30, and wherein at least about 50% of the peptoid region - (Q) n_ includes N-substituted glycines, always that the peptoid region - (Q) n- comprises at least one subregion selected independently from: (a) -AABA-; (b) -AABAB- (c) -ABACC; (d) -AAAAA-; (e) -ABCBA-; (f) -AABCA- or (g) -ABABA-; wherein A, B and C are each different N-substituted glycines. In some embodiments, Xa is acyl of (C? -C6) or aminoacyl of (Ci-β), each optionally substituted by a conjugated portion that is optionally linked through a linker portion. In some embodiments, Xa is acyl of (Ci-Cß) or aminoacyl of (Ci-β), each optionally substituted by a conjugated portion selected from an interlacing reagent or linkage each optionally linked through a linker portion. In some embodiments, Xa is acyl of (C? _C6) or aminoacyl of (C? -6), each optionally substituted by a selected conjugated portion of biotin or mercapto, wherein the conjugated portion is optionally attached through a portion linker In some embodiments, Xb is an amino acid optionally substituted by a conjugated moiety that is optionally linked through a linker moiety.

In some embodiments, Xb is amino, alkylamino, dialkylamino. In some modalities, X is amino. In some modalities, n is approximately 5 to about 15; 5 to about 10; or 6. In some embodiments, n is 4 to 10, 4 to 8, 5 to 7 or 6. In some embodiments, Xb is an amino acid optionally substituted by a conjugated portion and n is 6. In some embodiments, the linking portion contains a region that has the formula -. { NH (CH2) mC (O)} p-. In some modalities, m is 1 to 10. In some modalities, m is 1 to 8. In some modalities, m is 5. In some modalities, p is 1 to 5. In some modalities, p is 1 to 3. In some embodiments, p is 1 or 2. In some embodiments, Xb is an amino acid optionally substituted by a conjugated moiety that is optionally linked through a linker moiety, and n is 6. In some embodiments, Xb is amino, alkylamino or dialkylamino; Xa is H, (C? -C6) alkyl, (C? -C6) acyl, (C? _6) aminoacyl, an amino acid, or an amino protecting group, wherein Xa is optionally substituted by a conjugated moiety which is optionally linked through a linker moiety and n is 6. In some embodiments, Xb is amino, alkylamino or dialkylamino; Xa is H, alkyl of (C? _C6), acyl of (C? -C6), aminoacyl of (C? -6, an amino acid or an amino protecting group, wherein Xa is replaced by a conjugated portion selected from an agent of entanglement or binding agent, wherein the conjugated portion is optionally linked through a linker moiety and n is 6. In some embodiments, Xb is amino, alkylamino or dialkylamino, Xa is H, (C? -C6) alkyl, acyl (Ci-Cß), aminoacyl of (C? -6, an amino acid or an amino protecting group, wherein Xa is replaced by a conjugated portion comprising biotin or mercapto, wherein the conjugated portion is optionally attached through a linker portion and wherein at least a portion of the linker portion has the formula -. {NH (CH2) mC (O).}. p-; n is 6; m is 1 to 10; and p is 1 to 5; In some embodiments, each Q is independently an amino acid or an N-substituted glycine having the formula - (NR-CH2-C0) - wherein each R is selected independently of (C2-C6) alkyl, (Ci-Cß) haloalkyl, (C2-C6) (C2-C6) alkenyl, (C6-C6) cycloalkyl-aryl, (C-C6) aminoalkyl, ? -C6), ammonioalkyl of (Ci-Cd), hydroxyalkyl of (C? ~ C6), alkoxy of (C? -C6) -alkyl of (C? ~ C6), carboxy, carboxyalkyl of (C2-C6), carbamylalkyl of (C2-Ce), guanidino, guanidinoalkyl of (C? -C6), amidinoalkyl of (C? -C6), thiol, alkylthiol of (C? C6), alkylthioalkyl of 2-10 carbon atoms, heterocyclyl contains N, heterocyclylalkyl of (C? ~ C6) containing N, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms and arylalkyl of (C? ~ C6); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (Ci-Cß) alkoxy. In some embodiments, each Q is independently an amino acid or an N-substituted glycine having the formula - (NR-CH2-C0) - wherein each R is independently selected from alkyl of (C2-Ce), haloalkyl of Cß), (C2-C6) alkenyl, (C2-Cd) alkynyl, (C6-C? 0) cycloalkylaryl, (C? -C6) aminoalkyl, (C? -C6) hydroxyalkyl, C? -C6) -alkyl of C? -C6), carboxy, carboxyalkyl of (C2-Ce), carbamyl, carbamylalkyl of (C2-C6), guanidino, guanidinoalkyl of (C? -C6), thiol, alkaliol of ( C? -C6), alkylthioalkyl of 2-10 carbon atoms, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyl-alkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, diphenylalkyl of (Ci-Ce) or arylalkyl of (C? -C6); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C? -C6) alkoxy. In some embodiments, each Q is independently an amino acid or an N-substituted glycine of the formula - (NR-CH2-CO) - wherein each R is independently selected from (C2-C6) alkyl, aminoalkyl of (C? ~ Ce), hydroxyalkyl of (Ci-Cd), alkoxy of (C? -C6) -alkyl of (Ci-Cd), guanidinoalkyl of (Ci-Cß), indolyalkyl of 9-15 carbon atoms, naphthylalkyl of 11-16 carbon atoms, diphenylalkyl of (Ci-Cß) or arylalkyl of (Ci-Cß), substituted with 1-3 substituents independently selected from halogen, hydroxy or (C? -C6) alkoxy. In some embodiments, each Q is independently an amino acid or is an N-substituted glycine selected from N- (4-aminobutyl) glycine, N- (1-phenylethyl) glycine, N- (2-aminoethyl) glycine, N- (2- [4-methoxyphenyl] ethyl) glycine, N- (2-methoxyethyl) glycine, N- (2-hydroxyethyl) glycine, N- ((lH-indol-3-yl) methyl) glycine or N -benzylglycine. In some embodiments, each Q is independently an amino acid or is an N-substituted glycine selected from N- (4-aminobutyl) glycine or N-benzylglycine. In some embodiments, each Q is independently an N-substituted glycine. In some embodiments, the peptoid region - (Q) n - comprises at least 3 or at least 4 N-substituted glycines which are charged at physiologically relevant pH. In some modalities, the load is positive. In some embodiments, the remaining terminal N-substituted glycins of the peptoid region are neutral at physiologically relevant pH. In some embodiments, the peptoid region - (Q) n ~ comprises 2 to 6, 3 to 5 or 4 N-substituted glycines which are charged at a physiologically relevant pH. In some modalities, the load is positive. In some embodiments, the remaining N-substituted glycines of the peptoid region are neutral at physiologically relevant pH. In some embodiments, two N-substituted glycine residues of the peptoid region - (Q) n are positively charged at physiologically relevant pH and the remaining N-substituted glycine residues of the peptoid region are neutral at physiologically relevant pH. In some embodiments, four glycine residues N-substituted from the peptoid region - (Q) n- are positively charged at physiologically relevant pH and the remaining N-substituted glycine residues from the peptoid region are neutral at a physiologically relevant pH. In some embodiments, five glycine residues N-substituted from the peptoid region - (Q) n are positively charged at physiologically relevant pH and the remaining N-substituted glycine residues from the peptoid region are neutral at a physiologically relevant pH. In some embodiments, the peptoid region - (Q) n- is poly-ionic at a physiologically relevant pH. In some embodiments, the peptoid - (Q) n region is polycationic at physiologically relevant pH. In some embodiments, the peptoid region - (Q) n_ is polymeric at a physiologically relevant pH. In some embodiments, the peptoid region - (Q) n_ has a net charge of at least 3+ at physiologically relevant pH. In some embodiments, the peptoid region - (Q) n_ has a net charge of at least 4+ at physiologically relevant pH. In some embodiments, the peptoid region - (Q) n_ has a net charge of 2+ to 6+ at physiologically relevant pH. In some embodiments, the peptoid - (Q) n- region has a net charge of 3+ to 5+ at physiologically relevant pH. In some embodiments, the peptoid - (Q) n- region has a net charge of 4+ at physiologically relevant pH. In some embodiments, the peptoid region - (Q) n ~ comprises at least 3 N-substituted glycines which are positively charged at physiologically relevant pH. • In some embodiments, the peptoid region - (Q) n_ comprises at least 4 N-substituted glycines that are positively charged at a physiologically relevant pH. In some embodiments, the peptoid region - (Q) n- comprises from 2 to 6 N-substituted glycines which are positively charged at physiologically relevant pH. In some embodiments, the peptoid - (Q) rila region peptoid comprises from 3 to 5 N-substituted glycines which are positively charged at a physiologically relevant pH. In some embodiments, the peptoid - (Q) n- region comprises N-substituted glycines which are also preferably charged at a physiologically relevant pH. In some embodiments, the N-substituted glycines of the peptoid - (Q) n- region have the formula - (NR-CH-C0) -, wherein R is independently selected from (C2-C6) alkyl, C-haloalkyl ? -C6), alkenyl of (C2-C6), alkynyl of (C2-C6), cycloalkyl-aryl of (C6-C? 0), aminoalkyl of (C? ~ C6), ammonioalkyl of (C? -C6) , (C 1 -C 6) hydroxyalkyl, (Ci-Cβ) alkoxy (Ci-Cß) alkyl, carboxy, (C 2 -C 6) carboxyalkyl, carbamyl, (C 2 -C 6) carbamylalkyl, guanidino, guanidinoalkyl (Ci-Ce), amidino, amidinoalkyl of (C? ~ C6), thiol, alkylthiol of (C? -C6), alkylthioalkyl of 2-10 carbon atoms, heterocyclyl containing N, heterocyclylalkyl of (C? ~ C6) containing N, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms, and arylalkyl of (Ci-Cß); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C? -C6) alkoxy, and the peptoid region - (Q) n ~ comprises at least 3, at least 4.2, a 6, 3 to 5 or 4 N-substituted glycines wherein r is a portion that is charged at a physiologically relevant pH. In some embodiments, all the N-substituted glycines of the peptoid region are contiguous. In some embodiments, the peptoid reagent comprises at least one conjugated portion. In some embodiments, the peptoid reagent comprises at least one conjugated portion linked through a linker portion. The invention further provides a peptoid reagent that preferably interacts with a pathogenic form of a conformation disease protein compared to a non-pathogenic form of the conformation disease protein wherein the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region and at least one peptoid region between the amino-terminal region and the carboxy-terminal region wherein the peptoid region comprises about 3 to about 30 N-substituted glycines and optionally one or more amino acids. In some embodiments, the peptoid region comprises from about 4 to about 30 or about 5 to about 30 N-substituted glycines. In some embodiments, the peptoid region comprises from about 4 to about 30, or about 5 to about 30 N-substituted glycines and a peptoid sub-region selected from: (a) -AABA-; (b) -AABAB- (c) -ABACC; (d) -AAAAA-; (e) -ABCBA-; (f) -AABCA- or (g) -ABABA-; wherein A, B and C are each different glycines N-substituted, and each sub-region sequence is read from left to right in the amino-terminal to carboxy-terminal direction. In some embodiments, the peptoid region comprises from about 50 to about 100%, about 75 to about 100%, or 100% N-substituted glycines. In some embodiments, the peptoid region has about 5 to about 50, about 5 to about 30, about 5 to about 15, about 5 to about 7 or 6 subunits long. In some embodiments, the peptoid reagent has a total length of about 5 to about 50, about 5 to about 30, about 5 to about 15 or about 6 to about 9 subunits. In some embodiments, at least one peptoid region is greater than about 50%, greater than about 75%, or greater than about 90% of the total length of the peptoid reagent. In some embodiments, all N-substituted glycines are contiguous in the peptoid region. In some embodiments, the N-substituted glycins of the peptoid region have the formula - (NR-CH2-CO) - wherein R is as defined throughout the present. In some embodiments, the peptoid region is poly-ionic at physiologically relevant pH and has characteristics according to any of the embodiments described herein throughout for charged peptoid regions.

The present invention further provides a peptoid reagent that preferably interacts with a pathogenic form of a conformation disease protein as compared to a non-pathogenic form of the conformation disease protein, wherein the reagent comprises a peptoid region comprising 3 to 15 contiguous N-substituted glycines, and wherein the peptoid region has a net charge at physiologically relevant pH. In some embodiments, the net charge is the net positive charge such as a net charge of at least 3+ or at least 4+ at a physiologically relevant pH. In some embodiments, the net charge is a net positive charge such as a net charge of at least 3+ or at least 4+ at a physiologically relevant pH. In some embodiments, the peptoid reagent itself has a net charge of 2+ to 6+, 3+ to 5+ or 4+ at physiologically relevant pH. In some embodiments, at least two, at least 3, or at least 4 of the contiguous N-substituted glycines of the peptoid region are charged at physiologically relevant pH. In further embodiments, at least two of the contiguous N-substituted glycines of the peptoid region comprise at least a portion selected from primary amino, secondary amino, tertiary amino, ammonium (amino quaternary), guanidino, amidino or heterocyclyl containing N.

In still further embodiments, at least two of the contiguous N-substituted glycines of the peptoid region comprise at least one N substituent selected from primary amino, secondary amino, ammonium, guanidino, amidino or N-containing heterocycle. In other additional embodiments, at least two of the contiguous N-substituted glycines comprise a substituent N, which is a group R according to the definitions provided herein. In other additional embodiments, the peptoid reagent comprises a peptoid region of 6 contiguous N-substituted glycines and the peptoid reagent itself has a net charge of 3+ or 4+ at physiologically relevant pH. The invention also provides methods for making peptoid reagents and for using peptoid reagents to detect pathogenic prion proteins, methods for the isolation of pathogenic prion proteins using peptoid reagents, methods for removing or reducing pathogenic prion proteins from samples and kit They contain component to carry out the different methods. A "peptoid reagent" refers to a peptoid molecule having an amino-terminal region, a carboxy-terminal region and at least one "peptoid region" between the amino-terminal region and the carboxy-terminal region. The amino-terminal region refers to a region on the amino-terminal side of the reagent that typically does not contain any N-substituted glycine. The amino-terminal region can be H, alkyl, substituted alkyl, acyl, an amino protecting group, an amino acid, a peptide or the like. In some embodiments, the amino-terminal region corresponds to Xa. The carboxy-terminal region refers to a region at the carboxy-terminal end of the peptoid that does not contain any N-substituted glycine. The carboxy-terminal region can include H, alkyl, alkoxy, amino, alkylamino, dialkylamino, a carboxy protecting group, an amino acid, a peptide or the like. In some embodiments, the carboxy-terminal region corresponds to Xb. In some embodiments, the peptoid reagent has a total length of about 5 to about 50 subunits; about 5 to about 30 subunits; about 5 to about 15 subunits or about 6 to about 9 subunits. In some embodiments, the peptoid reagent is a carboxy-terminal amide. The peptoid region generally refers to a portion of the peptoid reagent in which at least three of the amino acids there are replaced by N-substituted glycines. The "peptoid region" (also designated "- (Q) n_" herein) can be identified as the region that starts with and includes the N-substituted glycine closest to the amino terminus and which concludes with and includes the N-substituted glycine closest to the carboxy term. In some embodiments, the peptoid region comprises at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 99% or at least 100% N-substituted glycines. In some embodiments, the peptoid region comprises from about 25 to about 100%, about 50 to about 100%, about 75 to about 100% N-substituted glycines. In some embodiments, the peptoid region comprises 100% N-substituted glycines. In some modalities, the peptoide region has more than about 50% (for example around 50-100%) of the total length of the peptoid reagent. In some embodiments, the peptoid region is greater than about 60% (eg, about 60-100%) of the total length of the peptoid reagent. In some embodiments, the peptoid region is greater than about 75% (eg, about 75-100%) of the total length of the peptoid reagent. In some embodiments, the peptoid region is greater than about 90% (eg, about 90-100%) of the total length of the peptoid reagent. In some embodiments, the peptoid region has 100% of the total length of the peptoid reagent.

In some embodiments, the peptoid region comprises at least 3 N-substituted glycines. In some embodiments, the peptoid region comprises at least 4 N-substituted glycines. In some embodiments, the peptoid region comprises at least 5 N-substituted glycines. In some embodiments, the peptoid region comprises at least 6 N-substituted glycines. In some embodiments, the peptoid region comprises 3 to about 30, about 5 to about 30 N-substituted glycines; and optionally one or more amino acids. In some embodiments, the peptoid region has about 5 to about 50, 5 to about 30, 5 to about 15, 5 to about 10, 5 to about 9, 5 to about 8 or 5 to about 7 subunits long. . In some embodiments, the peptoid region has about 3, 4, 5, 6, 7, 8, 9 or 10 subunits long. In some embodiments, the peptoid region has 6 subunits long. In some embodiments, all the N-substituted glycines in the peptoid region are contiguous. In some embodiments, all subunits of the peptoid region are N-substituted glycines. In further embodiments, the peptoid reagent comprises a peptoid region of 4 to 12, 4 to 10, 4 to 9, 4 to 8, 5 to 7 or 6 contiguous N-substituted glycines. According to some embodiments, the peptoid region can be poly-ionic at physiologically relevant pH. By the term "poly-ionic" it is meant that the peptoid region comprises two or more residues that are charged at a physiologically relevant pH. In some embodiments, the peptoid region is polycationic or polyanionic at physiologically relevant pH. In additional embodiments, the peptoid region has a net charge of at least 3+ or at least 4+ at a physiologically relevant pH. In additional modalities, the peptoid region has a net charge of 2+ to 6+, 3+ to 5+ or 4+ at physiologically relevant pH. Non-limiting examples of N-substituted glycine residues that are charged include N- (5-aminopentyl) glycine, N- (4-aminobutyl) glycine, N- (3-aminopropyl) glycine, N- (2-aminoethyl) glycine , N- (5-guanidinopentyl) glycine, N- (4-guanidinobutyl) glycine, N- (3-guanidinopropyl) glycine and N- (2-guanidinoethyl) glycine. In some embodiments, the peptoid region comprises at least 3 or at least 4 N-substituted glycines that are positively charged at physiologically relevant pH. In some embodiments, the peptoid region comprises from 2 to 6, 3 to 5 or 4 N-substituted amino glycines which are positively charged at physiologically relevant pH. In some embodiments, the peptoid region comprises residues having the formula - (NR-CH2-C0) - wherein at least 3, at least 4.2 to 6.3, or 5 of the residues are loaded at physiologically relevant pH. In some embodiments, the charged residues of the peptoid region have the formula - (NR-CH2-CO) - wherein R is independently selected from aminoalkyl of (Ci-Cß), ammonioalkyl of (Ci-Cß), guanidino, guanidinoalkyl (C? ~ Cß), amidinoalkyl of (Ci-Cß), heterocyclyl containing N and heterocyclylalkyl of (Ci-Ce) containing N, wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, methoxy of C? ~ C3, and C? ~ C3 alkyl. In some embodiments, R is aminoalkyl of (Ci-Cß) such as aminobutyl. In some modalities, the peptoid reagent has a net charge of at least 3+ or at least 4+ at a physiologically relevant pH. In other additional embodiments, the peptoid reagent has a net charge of 2+ to 6+, 3+ to 5+ or 4+ at physiologically relevant pH. The peptoid region of the peptoid reagent comprises at least one peptoid subregion, which refers to a sequence of contiguous N-substituted glycines of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 or more waste. In some modalities, the peptoid region comprises at least one peptoid subregion selected independently of: (a) -AABA-; (b) -AABAB- (c) -ABACC; (d) -AAAAA-; (e) -ABCBA-; (f) -AABCA- or (g) -ABABA-. A, B and C each represent different N-substituted glycines. For example, each A occurring in the subregion refers to a particular N-substituted glycine, and each B occurring in the subregion refers to another particular N-substituted glycine, but A and B are different from each other. Accordingly, C is an N-substituted glycine that is different from either A or B. The sequence of the subregion is intended to be read from left to right in the amino to carboxy direction. In some embodiments, when A is a hydrophobic residue, then B is a hydrophilic and vice versa. In some embodiments, the peptoid subregion is homogeneous, that is, it comprises only one type of N-substituted glycine. In some embodiments, when A is an aliphatic residue, it is a cyclic residue. In some embodiments, when B is an aliphatic residue A is a cyclic residue. In some modalities, both A and B are aliphatic. In some modalities, A and B are aliphatic and C is cyclic. In some embodiments, all N-substituted glycines are aliphatic such as for the subregion -AABA-, for example, - (N- (2-methoxyethyl) glycine) 2-N- (4-aminobutyl) glycine- (N- ( 2-methoxyethyl) glycine) -, where A is N- (2-methoxyethyl) glycine and B is N- (4-aminobutyl) glycine. In some embodiments, the peptoid region comprises a tripeptoid, ie, three contiguous N-substituted glycines. The exemplary tripeptoid peptoid subregions include - (N- (2- (4-hydroxyphenyl) ethyl) glycine) 2-N- (4-guanidinobutyl) glycine-, -N- (4-aminobutyl) glycine- (V) 2-, wherein V is N-benzylglycine or N- (2-methoxyethyl) glycine, -N-benzylglycine-WN-benzylglycine-, wherein W is N- (4-aminobutyl) glycine or N- (2-methoxyethyl) glycine and - N- (4-aminoethyl) glycine- (N- (2- (4-methoxyphenyl) ethyl) glycine) 2-. In some embodiments, the tripeptoid subregion comprises at least one aliphatic and one cyclic residue, for example, (A) 2-B, B2-A or B-A-B where A is an aliphatic residue and B is a cyclic residue. In some embodiments, the peptoid subregion is a dipeptoid such as an N- (4-aminobutyl) glycine- (S) -N- (1-phenylethyl) glycine. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240 or 241, shown below. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 229, 230, 232, 233, 234, 235, 237, 238, 239 or 240. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 229, 230, 235, 237, 238, 239 or 240. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 230, 237, 238, 239 or 240. In some embodiments, the invention comprises reagent peptoid I, II, VII, IX, X, Xla, Xlb, Xlla or Xllb. In some embodiments, the invention comprises peptoid reagent II, IX, X, Xla, Xlb, Xlla or Xllb. The peptoid reagents of the invention can be engineered in concept by replacing amino acids of a fragment or peptide of a conformation disease protein with N-substituted glycines. Preferably, the parent peptide fragment is capable of binding to a conformation disease protein. Exemplary progenitor peptide fragments include those having the sequences of SEQ ID Nos: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 , 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 , 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 , 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103 , 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128 , 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170 , 171, 172, 173, 174, 175, 176, 177, -178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227 and 228. In some embodiments, at least one non-proline residue of the peptide fragment is replaced by an N-substituted glycine to form the peptoid reagent. In some embodiments, at least three amino acid residues of the peptide fragment are each replaced by N-substituted glycines to form the peptoid reagent. In some embodiments, at least five amino acid residues are replaced by N-substituted glycines. In some embodiments, the conformation disease protein is a prion protein. For example, the peptide fragment can be derived from any of those regions corresponding to residues 23-43 or 85-156 (eg, 23-30, 86-111, 89-112, 97-107, 113-135 and 136). -156) numbered according to the mouse prion sequence shown in SEQ ID NO: 2 of the co-owned patent applications US serial number 10 / 917,646, filed August 13, 2004, serial No. E.U.A. 11 / 056,950, filed on February 11, 2005 and international application PCT / US2004 / 026363, filed on August 13, 2004, all entitled "Specific Peptide Reagents of Prions", each of which are incorporated herein by reference. whole. In some embodiments, the peptide fragment is selected from any of SEQ ID Nos: 14, 50, 51, 52, 12, 72, 68 or 115 to 219. In some embodiments, the peptide fragment is selected from any of SEQ ID Nos: 14, 50, 51, 52 or 161 to 219. In some embodiments, the peptide fragment is selected from any of SEQ ID Nos: 12, 72, 68 or 115 to 160. In some embodiments, the peptide fragment is selected from any of SEQ ID Nos: 14, 50 or 68. As a starting point, the amino acid residues in the peptide fragment can be replaced with N-substituted glycines according to a replacement scheme in which the hydrophobic amino acid residues are replaced with N-substituted hydrophobic glycines and the hydrophilic amino acid residues are replaced with hydrophilic N-substituted glycines. In some embodiments, amino acid monomers of peptides can be replaced with N-substituted glycines according to the following replacement scheme to form a modified peptide: (a) Ala, Gly, Lie, Leu, Pro and Val can be replaced by N - (alkyl) glycine, N- (aralkyl) glycine or N- (heteroarylalkyl) glycine; (b) Asp, Asn, Cys, Gln, Glu, Met, Ser and Thr can be replaced by N- (hydroxyalkyl) glycine, N- (alkoxy) glycine, N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine; (c) Phe, Trp and Tyr can be replaced by N- (aralkyl) glycine, N- (hteroarylalkyl) glycine, N- (hydroxyaralkyl) glycine or N- (alkoxyalkyl) glycine; and (d) Arg, His and Lys can be replaced by N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine. The modified peptide can be evaluated for binding to the pathogenic form of a prion protein according to the methods described herein. Additional replacements, according to the above scheme, of amino acid monomers with N-substituted glycines can be made and retested until an adequate binding is obtained (i.e., peptoid reagents that preferably interact with the pathogenic form of the prion) . The methods for making peptoids are described in the U.S. Patents. Nos. 5,811,387 and 5,831,005, each of which is hereby incorporated by reference in its entirety, as well as the methods described herein. A peptoid reagent of the invention comprises monomers, multimers, cyclized molecules, branched molecules, linkers and the like. Multimers (ie, dimers, trimers and the like) of any of the sequences described herein or biologically functional fragments thereof are also contemplated. The multimer can be a homomultimer, ie, composed of identical monomers, for example, each monomer is the same peptoid sequence as SEQ ID NO: 229, below. Alternatively, the multimer can be heteromultimer, that is, all the monomers comprising the multimer are not identical. The multimers may be formed by direct attachment of the monomers to each other or to a substrate including, for example, various antigenic peptides (MPAS) (eg, symmetric MAPS), peptides attached to polymeric scaffolds, eg, a PEG scaffold and / or peptides linked in tandem with or without separating units. Alternatively, a linker can be added to the monomers to join them and form a multimer. Non-limiting examples of multimers using linkers include, for example, tandem repeats using glycine linkers, MAPS linked via a linker to a substrate and / or peptides linked linearly via linkers to a scaffold. The linker portions may involve the use of bifunctional separating units (either homobifunctional or heterobifunctional) such as those known to one skilled in the art. In some embodiments, the peptoid reagent interacts with the conformation disease protein of a prion-related disease, wherein the pathogenic form of the conformation disease protein is PrPSc, and the nonpathogenic form of the conformation disease is PrPc. In some embodiments, the peptoid reagent is specific for PrPSc of more than one species, for example, the peptoid reagent may be specific for prion protein of two or more species of human, cow, sheep, deer, elk, goat, mouse or hamster . In some embodiments, the peptoid reagent is specific for single-species PrPSc. In some embodiments, the peptoid reagent interacts with the pathogenic form of the conformation disease protein with an affinity of at least about 2-fold; 5 times; 10 times; 20 times; 50 times; 100 times; 200- times; 500 times or 1,000 times more than that for the non-pathogenic form of the conformation disease protein. In some embodiments, the affinity is at least about 10 times greater than that for the non-pathogenic form of the conformation disease protein. In some modalities, the affinity is at least 100 times greater. The invention further provides a complex comprising one or more peptoid reagents as described herein and a prion protein. In some modalities, the complex comprises a peptoid reagent described herein and a pathogenic prion. In some embodiments, the pathogenic prion is PrPSc. In some embodiments, the complex comprises the pathogenic prion and / or a peptoid reagent, prion binding reagent or ligand, which is optionally labeled. As used herein, the term "complex" means an association between prion, pathogen or non-pathogen and a peptoid reagent and / or prion binding reagent. Thus, a complex is not necessarily an association between a prion and a peptoid reagent, and may be an association between a prion and a prion binding reagent. The molecules in the complex will be linked together by sufficient intermolecular forces, ie, ionic, hydrophobic, hydrogen bonding, van der Waals, etc., to enable the complex to function as a single unit for the purposes of the methods and compositions described herein.

Compositions The present invention further provides a composition comprising a peptoid reagent of the invention, as described herein. In some embodiments, the composition comprises a peptoid reagent and a sample such as a biological sample. The biological sample is a sample prepared from a living organism or at some time alive. Non-limiting examples of biological samples are organs (eg, brain, liver and kidney), cells, whole blood, blood fractions, blood components, plasma, platelets, serum, cerebrospinal fluid (CSF), brain tissue, nervous system tissue , muscle tissue, muscle and fat tissue (eg, meat), bone marrow, urine, tears, non-nervous system tissue, foods that originate from a living or sometimes living organism such as beef, pork or venison and any other organic matter such as vegetables. The biological sample can be obtained by a health related procedure such as a blood donation or screening, biopsy, autopsy or necropsy, or during a process or procedure during the preparation of food such as a selection of animals and slaughterhouse and the assurance tests to ensure the quality of the finished product. The invention also provides a composition comprising a solid support and at least one peptoid reagent of the invention. The solid support can be, for example, nitrocellulose, polystyrene, polypropylene, latex, polyvinyl fluoride, diazotized paper, nylon membranes, activated spheres and / or magnetic response spheres, or polyvinyl chloride; polypropylene, polystyrene latex, polycarbonate, nylon, dextran, chitin, sand, silica, pumice, random, cellulose, glass, metal, polyacrylamide, silicon, rubber or polysaccharides; diazotized paper; or any other material used for solid phase synthesis, affinity separations, purifications, hybridization reactions, immunoassays and other such applications. The support can be a particulate material or it can be in the form of a continuous surface and includes membranes, mesh, plates, granules, slides, disks, capillaries, hollow fibers, needles, pins, fragments, solid fibers, gels (for example gels) silica) and spheres (e.g., pore glass spheres, silica gels, polystyrene spheres optionally entangled with divinylbenzene, grafted co-polymer spheres, polyacrylamide spheres, latex spheres, dimethylacrylamide spheres optionally crosslinked with NN '- bis-acryloylethylenediamine, magnetic spheres of iron oxide and glass particles coated with a hydrophobic polymer). In some of these embodiments, the solid support is selected from the group consisting of nitrocellulose, polystyrene latex, polyvinyl fluoride, diazotized paper, nylon membranes, activated spheres and magnetic response spheres. In some embodiments, the composition comprising the peptoid reagent is a pharmaceutical composition, ie, pharmaceutically acceptable and pharmacologically acceptable. In some embodiments, the composition further comprises at least one pharmaceutically acceptable carrier or excipient. The pharmaceutical carrier can be a solid or liquid. A solid carrier may include one or more substances which may also act as a flavoring agent, sweetening agent, lubricant, solubilizer, suspending agent, filler, glidant, compression aid, binder or tablet disintegrating agent; It can also be an encapsulation material. In powders, the carrier comprises a finely divided solid that is mixed with the finely divided peptoid reagent. Suitable carriers are typically large, slowly metabolized macromolecules such as proteins, polysaccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, lipid aggregates (such as drops or oil liposomes) and inactive virus particles. These vehicles are well known by those of ordinary skill in the art. An excipient is an ingredient that provides volume, imparts satisfactory processing and understanding characteristics, helps to control dissolution speed and / or otherwise provides desirable additional physical characteristics to the core material. The excipients, for example, are diluents, binders, lubricants and disintegrants well known to those of ordinary skill in the art, as described, for example, in Handbook of Pharmaceutical Excipients, American Pharmaceutical Association, Washington, D.C. and The Pharmaceutical Society of Great Britain, London, England (1986), incorporated herein by reference in its entirety. Suitable excipients include, for example, cellulosic material such as, Hypromellose, HPC, HEC, carboxymethylcellulose, microcrystalline cellulose, ethylcellulose, methylcellulose and its derivatives and salts; other organic compounds such as PEG, talc, lactose and other sugars, such as sucrose, glucose, fructose, maltose, and maltodextrin, acacia, dextrin, alginic acid, ethylcellulose resin, gelatin, guar gum, methylcellulose, pregelatinized starch, alginate sodium, starch, zein, polyvinylpyrrolidone, vinylpyrrolidine-vinyl acetate copolymer, vinyl acetate-protonic acid copolymer and ethyl acrylate-methacrylic acid copolymer. Plasticizers such as propylene glycol, glycerin, trimethylolpropane, PEG polymers, dibutyl sebacate, acetylated monoglycerides, diethyl phthalate, triacetin, glyceryl triacetate, acetyltriethyl citrate and triethyl citrate and lubricants, such as talc, magnesium stearate, calcium stearate , stearic acid, hydrogenated vegetable oils, magnesium lauryl sulfate, sodium benzoate, a mixture of sodium benzoate and sodium acetate, sodium chloride, leucine and Carbowax® 4000. A pharmaceutical composition of the invention can also be administered in conjunction with other molecules, for example, antigens and immunoregulatory agents such as immunoglobulins, cytokines, lymphokines and chemokines, including but not limited to interieukin 2 (IL-2), modified IL-2 (cysl25-serl25), granulocyte colony-stimulating factor and macrophages (GM-CSF), interieucin 12 (IL-12), alpha- or gamma-interferon, chemokine IP-10 and β chemokines such as RAN TES, MlPI-a, and MlPI-ß. When administered as a whole, the composition can be administered simultaneously or sequentially with the other molecule and if simultaneously, either as a single dose unit such as a mixture comprising the composition of another molecule, or as separate and distinct dosage units. , each unit comprising either the composition or another molecule. The pharmaceutical compositions described herein may comprise a therapeutically effective amount of the peptoid reagent. As used herein, "therapeutically effective amount" means an amount that will induce a protective and / or therapeutic response in the uninfected, infected, exposed or unexposed animal such as a mammal, eg, human or non-human, at which is administered. A therapeutically effective amount will vary depending on the animal being treated, the age and general condition of the animal being treated, the ability of the animal's immune system to synthesize antibodies, the degree of protection desired, the severity of the condition being treated. treated, the particular composition selected and its mode of administration, among other factors. An ordinarily trained medical provider can determine the therapeutically effective amount, as well as, the appropriate dose and frequency of administration to achieve an optimal clinical outcome. For example, the composition of the invention may be administered in a single dose, or as part of an administration regimen such as multiple doses, and may be administered daily, weekly, monthly, annually, semi-annually, biannually and the like. A pharmaceutical composition can be administered by various means, for example, but not limited to, intramuscularly, intramuscularly, subcutaneously, intradermally, transdermally, transcutaneously, intravaginally, intraperitoneally, intrarectally, orally, nasally, rectely, ocularly, intestinally and / or intravenously. A composition may be adapted for administration; for example, for oral administration, it may be in the form of tablets or capsules, optionally enteric coating, liquid or controlled release tablets and for nasal administration, it may be in the form of a nasal spray, nasal drops, gel or powder. The dosage regimen may include a first dose and a second dose. The first dose such as an initial dose and a second dose such as a boost can be administered mucosally, parenterally or a combination thereof. Although examples of administration routes are provided, the appropriate administration route, and dosage, are generally determined on a case-by-case basis by the attending physician. These determinations are routine for someone of ordinary skill in the art (see, for example, Harrison's Principles of International Medicine (1998), Fauci et al., Eds., 14th ed., New York: McGraw Hill.).

Detection The present invention further provides methods for detecting the presence of prion proteins, particularly pathogenic prion proteins. The detection methods are based on the property of the peptoid reagents of the invention to interact preferably with pathogenic prion forms. Detection methods can be used, for example, with methods for detecting a conformation disease protein, especially a pathogenic prion protein, in a sample, methods for diagnosing a prion-related disease (e.g., in humans or non-human animals). , Methods for Securing a Blood Supply Substantially Free of PrPSc, Blood Products Source, or Food Source, Methods for Analyzing Organ and Tissue Samples for Transplant, Methods for Monitoring Decontamination of Surgical Tools and Kit, as Well as Any Other Situation in which the knowledge of the presence or absence of the pathogenic prion is important. Thus, the present invention relates to a method for the detection of the presence of a pathogenic prion in a sample, which comprises contacting the sample with a first reactive peptoid of the invention under conditions that allow the binding of the peptoid reagent to the pathogenic prion, if present to form a complex, and detect the formation of the complex, the formation of the complex being indicative of the presence of the pathogenic prion. Typical conditions that allow the binding of the peptoid reagent to the pathogenic prion are described in the examples herein. Other suitable bonding conditions can be readily determined by one of ordinary skill in the art. The method of detecting pathogenic prion in a sample may also comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, contacting the first complex with a second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex , the formation of the second complex being indicative of the presence of the pathogenic prion. The second complex may comprise the second peptoid reagent and the pathogenic prion, and optionally, the first peptoid reagent. In a further embodiment, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, removing any unbound sample. , contacting the first complex with a second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. The first peptoid reagent optionally comprises a solid support that aids separation of the first complex from the unbound sample. In addition, the detection method of the invention may comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, remove sample unbound, dissociate the pathogenic prion from the first complex thereby providing dissociated pathogenic prion, contacting the dissociated pathogenic prion with a second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the attachment of the second peptoid reagent to the prion pathogen dissociated to form a second complex, and detect the formation of the second complex, the formation of the second complex is an indicator of the presence of the pathogenic prion. The dissociation of the first complex can be achieved by any conventional method to break protein-binding interactions, for example, the addition of a salt or chaotropic agent, increase in temperature, addition of a detergent or denaturant and mechanical disruption, and can also comprise the treatment at a high or low pH as described herein.

The method of detecting the pathogenic prion in a sample may also comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, contacting the first complex with a prion binding reagent (described herein), optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the pathogenic prion. The second complex may comprise the prion binding reagent and the pathogenic prion, and optionally, the first peptoid reagent. In a further embodiment, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, removing any unbound sample. , contacting the first complex with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. The first peptoid reagent optionally comprises a solid support that aids separation of the first complex from the unbound sample. In addition, the detection method of the invention comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex, remove the sample unbound, dissociating the pathogenic prion from the first complex thereby providing a dissociated pathogenic prion, contacting the dissociated pathogenic prion with a prion binding reagent, optionally labeled in detectable form, under conditions that allow binding of the binding reagent prions to the dissociated pathogen prion to form a second complex, and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. In a further embodiment, the detection method of the invention may comprise contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex. , removing unbound sample, dissociating the pathogenic prion from the first complex thus providing dissociated pathogenic prion, contacting the dissociated pathogenic prion with a prion binding reagent under conditions that allow the binding of the prion binding reagent to the dissociated pathogenic prion for forming a second complex, and detecting the formation of the second complex using a second prion binding reagent, optionally labeled in detectable form, the formation of the second complex being indicative of the presence of the pathogenic prion. The dissociated pathogenic prion is preferably denatured during or after the dissociation of the first complex and before the formation of the second complex. Typically, the agents that effect dissociation of the pathogenic prion from the complex (eg, chaotropic agents, heat, high or low pH) will promote the denaturing of the pathogenic prion protein, however, it is desirable, that the dissociation of the pathogenic prion from the complex can be achieved without denaturing the protein, for example using a low concentration (eg, 0.4 to 1.0 M) of guanidinium hydrochloride or guanidinium isothiocyanate. See, WO200607497 (international application PCT / US2006 / 001090) for additional conditions to dissociate the pathogenic prion from the complex without denaturing the prion protein In another embodiment, the detection method comprises contacting the sample with a prion binding reagent under conditions that allow the binding of the prion binding reagent to the pathogenic prion, if present, to form a first complex, remove unbound sample, put in contact the complex with a peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, the formation of the second complex being an indicator of the presence of the pathogenic prion. The prion binding reagent is optionally provided on a solid support. In some embodiments, the dissociation step comprises contacting the bound pathogenic prion protein with a salt or chaotropic agent such as, for example, guanidinium thiocyanate (GdnSCN) or guanidinium hydrochloride (GdnHCl). Suitable exemplary concentrations of GdnSCN or GdnHCl are between about 3 M and about 6M. In some embodiments, the dissociation step comprises exposing the pathogenic prion protein bound to high or low pH, whereby the dissociated pathogenic prion protein is denatured. For example, the pH can be above 12 or below 2. In some embodiments, the pH is between 12.5 and 13.0. A high pH can be achieved by the addition of NaOH to form a concentration of 0.05 N to 0.15 N. Exposure to high or low pH can be carried out for no more than 15 minutes or no more than 10 minutes. In some embodiments, the high or low pH is neutralized to between 7.0 and 7.5 such as by the addition of phosphoric acid or a sodium salt thereof. A "prion binding reagent" is a reagent that binds to a prion protein in a certain conformation, for example, the prion binding reagent can bind to one or more of a denatured form of the prion protein, the PrPc form ( non-pathogenic isoform), or the PrPSc form (pathogenic isoform). Some of these prion binding reagents will bind to more than one of these forms of prion protein. Prion-binding reagents have been described and include, for example, anti-prion antibodies (described, inter alia, in Peretz et al., 1997 J. Mol. Biol. 273: 614; Peretz et al. 2001 Na ture 412: 739; Williamson et al. 1998 J. Virol. 72: 9413; Polymenidou et al. The Lancet 2005 4: 805; patent of E.U.A. No. 4,806,627; patent of E.U.A. No. 6,765,088 and US patent. No. 6,537548), hybrid polypeptides grafted to motifs (see, WO03 / 085086), certain cationic or anionic polymers (see, WO03 / 073106), certain peptides that are "propagation catalysts" (see, WO02 / 097444), prion-specific peptide reagents (see, for example, WO2006 / 076687 and US20060035242) and plasminogen. In all methods using a prion binding reagent, the prion binding reagents that are preferred are anti-prion antibodies. Moreover, the detection method may comprise providing a solid support comprising a peptoid reagent of the invention, combining the solid support with a labeled ligand in detectable form, wherein the peptoid reagent of the support has a weaker binding affinity for the ligand that for the pathogenic prion, to form a first complex, combine the sample with the first complex under conditions that allow the binding of the pathogenic prion, if present in the sample, to the peptoid reagent of the first complex, thereby replacing the ligand marked in detectable form of the first complex and forming a second complex comprising the peptoid reagent and the pathogenic prion, and detecting the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. For use in methods for detecting the presence of a pathogenic prion in a sample, the sample can be any known by, or suspected of, containing a pathogenic prion protein. In some embodiments, the sample is suspected of containing a pathogenic prion, for example, PrPSc. In some embodiments, the sample is a biological sample (ie, a sample prepared from a living organism or at some time alive), or a non-biological sample. In some modalities, the sample is a biological sample. Non-limiting examples of biological samples are organs (eg, brain, liver and kidney), cells, whole blood, blood fractions, blood components, plasma, platelets, serum, cerebrospinal fluid (CSF), brain tissue, nervous system tissue , muscle tissue, muscle and fat tissue (for example, meat, bone marrow, urine, tears, non-nervous system tissue, foods that originate from a living or sometimes living organism and any other organic matter such as plant materials. Some modalities, the biological sample includes whole blood, blood fractions, blood components, plasma, platelets or serum.In some modalities, the biological sample is obtained from a biopsy, autopsy or necropsy.In some modalities, the sample is not biological. Non-limiting examples of non-biological samples include pharmaceuticals, cosmetics of personal care products, and foods that do not originate from a living organism or Once I live, and similar. The sample can be pretreated in conventional ways (eg, heating, grinding, sonication, exposure to certain digestive enzymes) to ensure contact between the pathogenic prion protein that may be present in the sample and the peptoid reagent.

The detection methods of the invention can utilize any of the peptoid reagents described herein. In some embodiments, the detection method of the present invention utilizes a peptoid reagent that interacts with a protein in conformational disease such as a prion protein, preferably with a pathogenic-form as compared to a non-pathogenic form of the disease protein. of conformation, having a formula of: Xa- (Q) n-Xb wherein: each Q is independently an amino acid or an N-substituted glycine, and - (Q) n_ defines a peptoid region; Xa is H, (Ci-Cg) alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, acyl (C? -C6), aminoacyl (C? _6), an amino acid, an amino protecting group, or a polypeptide of 2 to about 100 amino acids, wherein Xa is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety; Xb is H, (C! -C6) alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (Ci-Cd) alkoxy, aryloxy, aralkoxy, a carboxy protective group, an amino acid , a polypeptide of 2 to about 100 amino acids, wherein Xb is optionally substituted by a conjugated moiety that is optionally linked through a linker portion, and n is 3 to about 30; wherein at least about 50% of the peptoid region - (Q) n_ comprises N-substituted glycines. In some of these embodiments, n is from about 4 to about 30, preferably from about 5 to about 30, and the peptoid region - (Q) n_ comprises at least one subregion selected independently of: (a) -AABA-; (b) -AABAB- (c) -ABACC-; (d) -AAAAA-; (e) -ABCBA-; (f) -AABCA- or (g) -ABABA-; wherein A, B and C are each different N-substituted glycines. In some embodiments of the detection method, the peptoid reagent comprises an amino-terminal region, a carboxy-terminal region and at least one peptoid region between the amino-terminal region and the carboxy-terminal region, wherein the peptoid region comprises from 3 to about 30 N-substituted glycines and optionally one or more amino acids. In some of these embodiments, the peptoid region comprises a peptoid subregion selected from: (a) -AABA-; (b) -AABAB- (c) -ABACC-, (d) -AAAAA-, (e) -ABCBA- (f) -AABCA- or (g) -ABABA-; wherein A, B and C are each different N-substituted glycines. In some embodiments of the detection method of the present invention, the peptoid reagent comprises a peptoid analogue of a 3 to 30 amino acid peptide fragment of the conformation disease protein, wherein the peptide fragment is selected from the group of sequences that consists of SEQ ID Nos. 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119; 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 135, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165 ', 166, 167, 168, 169 , 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194 , 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219 , 220, 221, 222, 223, 224, 225, 226, 227 and 228 wherein: (a) at least one non-proline residue of the peptide fragment is replaced by an N-substituted glycine to form the peptoid analogue or (b) at least five amino acid residues of the peptide fragment are each replaced by an N-substituted glycine to form the peptoid analogue. In some modalities of the previous method, the replacement of any one or more amino acid residues of the peptide fragment with an N-substituted glycine corresponds to the following replacement scheme: i) Ala, Gly, Lie, Leu, Pro and Val are replaced by N- (alkyl) glycine, N- (aralkyl) glycine or N- (heteroarylalkyl) glycine; ii) Asp, Asn, Cys, Gln, Glu, Met, Ser and Thr are replaced by N- (hydroxyalkyl) glycine, N- (alkoxy) glycine, N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine; iii) Phe, Trp and Tyr are replaced by N- (aralkyl) glycine, N- (heteroarylalkyl) glycine, N- (hydroxyaralkyl) glycine or N- (alkoxyalkyl) glycine and iv) Arg, His and Lys are replaced by N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine. In some of these embodiments, the peptoid reagent comprises a peptoid analogue of a peptide fragment of 5 to 30 amino acids of the conformation disease protein as described above. In some embodiments of the method for detecting the presence of a pathogenic prion in a sample, the peptoid reagent comprises a sequence as described herein, for example, having a sequence selected from the group consisting of SEQ ID Nos: 229, 230 , 231, 232, 233, 234, 235, 236, 237, 238, 239, 240 and 241. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 229, 230, 232, 233, 234, 235 , 237, 238, 239 or 240. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 229, 230, 235, 237, 238, 239 or 240. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NO: 230, 237, 238, 239 or 240. In some embodiments, the method of the invention utilizes one or more of peptoid reagent I, II, VII, IX, X, Xla, Xlb, Xlla or Xllb. In some embodiments, the method of the invention utilizes one or more of the peptoid reagent II, IX, X, Xla, Xlb, Xlla or Xllb. In some embodiments, the peptoid reagent used in the method comprises a sequence selected from SEQ ID Nos: 229, 236, 231, 232, 233, 234 or 235. In some embodiments, the peptoid reagent comprises a sequence selected from SEQ ID NOS: 230, 237, 238, 239 or 240. In some embodiments thereof, the peptoid reagent comprises SEQ ID NO: 230, 237 or 240. In some of these embodiments, the peptoid reagent comprises SEQ ID NO: 240. In some embodiments, The method for detecting the presence of a pathogenic prion in a sample comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a complex that understand the first peptoid reagent and the pathogenic prion protein, and detect the presence of the pathogenic prion, if any, in the sample by its binding to the first peptoid reagent. The binding of the pathogenic prion to the first peptoid reagent can be detected by detecting the formation of the complex, the formation of the complex being indicative of the presence of the pathogenic prion. In general, in preferred embodiments of the method, the complex comprising the first peptoid reagent and the pathogenic prion protein is separated from the rest of the sample (i.e., the unbound sample) before detection. The formation of the complex can be detected by detecting the pathogenic prion in the complex or by dissociating the complex (after its separation from the unbound sample) and detecting the dissociated pathogenic prion. The dissociated pathogenic prion may or may not be in the pathogenic conformation. In some embodiments, the dissociated pathogenic prion is in a denatured prion conformation. The dissociated pathogenic prion can be detected in ways that are known in the art, for example, by binding an anti-prion antibody that is specific to the appropriate prion isoform, and which is as described hereinafter. Antibodies recognizing different prion isoforms have been described in the art (see, for example, U.S. Patent Nos. 5,846,533, 6,765,088, 6,261,790, 4,806,627, 6,165,784, 6,528,269, EP891552, EP90388, Polymenidou et al., The Lancet 2005 4: 805). In a preferred embodiment of the above method, the pathogenic prion is dissociated from the complex with the peptoid reagent using a chaotropic agent, or using high or low pH treatment as described herein. In addition, the method for detecting a pathogenic prion in a sample by first forming a complex with the prion-specific peptoid reagent can be followed by detection of the complex with an analytical method. The analytical method may comprise a method such as UV / Visible spectroscopy, FTIR, nuclear magnetic resonance spectroscopy, Raman spectroscopy, mass spectroscopy, HPLC, capillary electrophoresis, surface plasmonic resonance spectroscopy, Micro-Electro-Mechanical Systems (MEMS) or any other method known in the art. In some embodiments, the peptoid reagent or the prion binding reagent comprises a detectable label. Detectable labels suitable for use in the invention include, for example, any molecule capable of detection, such as defined hereinbefore. In some embodiments, the label comprises an enzyme, radioisotope, toxin or fluorophore. In addition, the detectable label can include an oligonucleotide label, which can be detected by a nucleic acid detection method including, for example, polymerase chain reaction (PCR), transcription mediated amplification (TMA), DNA branched (b-DNA), amplification based on nucleic acid sequence (NASBA) and the like. Preferred detectable markers include enzymes, especially alkaline phosphatase (AP), horseradish peroxidase (HRP), and fluorescent compounds. As is well known in the art, the enzymes use in combination with a detectable substrate, for example, a chromogenic substrate or a fluorogenic substrate, to generate a detectable signal. In some embodiments of the detection methods of the invention, one or more peptoid reagents is attached to a solid support. A solid support, for the purposes of the invention, can be any material that is an insoluble matrix and can have a rigid or semi-rigid surface to which a molecule of interest (e.g., peptoid reagents of the invention, prion proteins, antibodies, etc.) can be linked or linked. Exemplary solid supports include, but are not limited to, those previously described herein. Peptoid reagents, such as those described herein, may be covalently attached to the support, or by absorption, coupling or use of binding pairs. For example, peptoid reagents can be easily coupled to the solid support using techniques well known in the art. Immobilization to the support can be increased by first coupling the peptoid reagent with a protein such as when the protein has better solid phase binding properties. Suitable coupling proteins include, but are not limited to, macromolecules such as serum albumins including bovine serum albumin (BSA), keyhole limpet hemocyanin, immunoglobulin molecules, thyroglobulin, ovalbumin and other proteins well known to those experts in the art. The peptoid reagents can also be attached to the solid support through the interaction of a molecule binding pair. One member of the binding pair is coupled to the solid support and the other member of the binding pair is attached to the peptoid reagent (before, during or after synthesis). For example, the support may comprise avidin or streptavidin and the peptoid reagent may comprise biotin. In addition to biotin-avidin and biotin-streptavidin, other binding pairs suitable for attaching the peptoid to the support include, without limitation, antigen-antibody, hapten-antibody, mimetopo-antibody, receptor-hormone, receptor-ligand, agonist-antagonist, lectin-carbohydrate, Protein A-Fe antibody. These binding pairs are well known (see, for example, U.S. Patent Nos. 6,551,843 and 6,586,193) and one of skill in the art would be competent to select the appropriate binding pairs and adapt them for use with the present invention. Alternatively, the peptoid reagents can be covalently bound to the solid support using conjugation chemistries that are well known in the art. Pitytoid reagents containing thiols are attached directly to solid supports, for example, carboxylated magnetic spheres, using standard methods known in the art (see, for example, Chrisey, LA, Lee, GU and O'Ferrall, CE. (1996) .Covalent Attachment of synthetic DNA to self-assembled monolayer films.Nucleic Acids Research 24 (15) ), 3031-3039; Kitagawa, T., Shimozono, T., Aikawa, T., Yoshida, T. and Nishimura, H. (1980). Preparation and characterization of hetero-bifunctional cross-linking reagents for protein modifications. Chem. Pharm. Bull. 29 (4), 1130-1135). The carboxylated magnetic spheres are first coupled to a heterobifunctional interlayer containing a maleimide functionality (BMPH from Pierce Biotechnology Inc.) using carbodiimide chemistry. The peptide or thiolated peptoid is then covalently coupled to the maleimide functionality of the beads coated with BMPH. When the embodiments of the detection methods of the invention are used, the solid support aids in the separation of the complex comprising the peptoid reagent of the invention and the pathogenic prion protein from the unbound sample. Particularly suitable magnetic spheres for thiol coupling are Dynabeads® of Dynal M-270 carboxylic acid. The peptoid reagent may also comprise a linker, for example, one or more portions of aminohexanoic acid. In some embodiments of the method for detecting the presence of a pathogenic prion in a sample, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present. , to form a first complex, then to contact the first complex with a second peptoid reagent labeled in detectable form of the invention under conditions that allow the attachment of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and then detect the binding of the pathogenic prion to the second peptoid reagent. In some embodiments, the binding of the pathogenic prion protein to the second peptoid reagent can be detected by detecting the formation of the second complex, the formation of the second complex being indicative of the pathogenic prion. In some embodiments, the peptoid reagents are different. In some embodiments, the first and second peptoid reagents are the same. In some embodiments, the first peptoid reagent comprises biotin. In additional embodiments, the first peptoid reagent is bound to a solid support. In some embodiments of the detection methods of the invention, the method comprises contacting the sample with a first peptoid reagent of the invention under conditions that allow the binding of the first peptoid reagent to the pathogenic prion, if present, to form a first complex; remove the unbound sample, which may include, for example, non-pathogenic prion present in the sample; dissociating the pathogenic prion from the first complex, thereby providing dissociated pathogen prion; contacting the dissociated pathogenic prion with a second peptoid reagent labeled in detectable form of the invention under conditions that allow the attachment of the second peptoid reagent to the dissociated pathogenic prion to form a second complex and detect the formation of the second complex, the formation of the second complex being indicative of the presence of the pathogenic prion. In this modality, the dissociated pathogenic prion retains the pathogenic conformation. In general, "dissociated pathogenic prion" or "dissociated prion" may include prion protein that retains the pathogenic conformation, as well as pathogenic prion protein that has been denatured, denatured prion that may not have either the pathogenic conformation or the normal cellular conformation, and it might not be infectious. Alternatively, when the peptoid reagents of the invention are used to directly capture the pathogenic prion protein to form a first complex and the first complex is separated from the unbound sample materials, as described above, a prion binding reagent, which is optionally labeled in detectable form, can be used to detect the pathogenic prion, either while the pathogenic prion is bound in the first complex or after the dissociation of the prion protein from the first complex. As previously mentioned in this, a prion binding reagent is a reagent that binds to a prion protein in some conformation, for example, the prion binding reagent can bind to one or more of a denatured form of the prion protein, the PrPc form ( non-pathogenic isoform), or the PrPSc form (pathogenic isoform). Some of these prion binding reagents will bind to more than one of these forms of prion protein. Prion-binding reagents have been described and include, for example, anti-prion antibodies (described, inter alia, in Peretz et al., 1997 J. Mol. Biol. 273: 614; Peretz et al. 2001 Na ture 412: 739; Williamson et al. 1998 J. Virol. 72: 9413; Polymenidou et al. The Lancet 2005 4: 805; patent of E.U.A. No. 4,806,627; patent of E.U.A. No. 6,765,088; and patent of E.U.A. No. 6,537548), hybrid polypeptides grafted to motifs (see, WO03 / 085086), certain cationic or anionic polymers (see, WO03 / 073106), certain peptides that are "propagating catalysts" (see, WO02 / 097444), prion-specific peptide reagents (see, for example, WO2006 / 076687 and US20060035242) and plasminogen. If the particular prion binding reagent used binds to a denatured form of the prion, it will be apparent that the pathogenic prion protein of the first complex must be denatured prior to detection with the prion binding reagent. The prion binding reagents, particularly anti-prion antibodies, can be selective for prion proteins of the particular animal species. Thus, it will be apparent that prion binding reagents will be selected that have suitable binding properties in terms of specificity for prion conformation and species specificity. The peptoid reagent of the invention can then be used either as a "capture" reagent for pathogenic prions in a sample or as a "detection" reagent for the captured pathogenic prion, or as the capture or detection reagent. When the peptoid reagent is used to capture the pathogenic prion, the captured prion can be removed from the rest of the sample (by virtue of the complex formed with the peptoid reagent) and the prion can be detected by conventional means (eg, ELISA, Western blot). , immunoprecipitation, etc.), either while complexed to the peptoid reagent or after dissociation of the complex. The captured prion can alternatively be detected using a second peptoid reagent that is detectably labeled.

ELISA A particularly preferred method for detecting a prion in a sample combines the use of the peptoid reagents of the invention with an improved ELISA technique. The assay combines the potency of peptoid reagents to discriminate between the pathogenic and nonpathogenic form of prion proteins with an improved ELISA technique. Because peptoid reagents interact with preferentially pathogenic prion proteins, these reagents are used to separate and concentrate any pathogenic prion present in the sample. Unlike methods that use proteinase K digestion to discriminate between pathogenic and nonpathogenic forms, which typically results in some N-terminal digestion even of the pathogenic isoform, the use of peptoid reagents in the method of the invention results in the separation of full-length pathogenic prion proteins. Thus, anti-prion antibodies that recognize epitopes at the N-terminus of the prion protein, for example, epitopes in the region of residues 23-90, can be used for detection, as well as anti-prion antibodies that recognize epitopes of other regions of the prion protein. The N-terminal region of the prion protein of most species contains a repeated sequence (4 copies of the octa-repeat GQPHGGGS / W or 5 copies in PrP of bovine). Antibodies that bind within this region can receive increased avidity resulting in increased sensitivity for the assay. Once the pathogenic prion protein is separated from the non-pathogenic isoform (which is present in many biological samples) using the peptoid reagents as described above, the pathogenic prion protein can be dissociated from the peptoid reagent and detected in a number of formats of ELISA, described herein. The pathogenic prion is typically denatured in the dissociation process of the peptoid reagent, although it does not necessarily do so. Denaturation of the PrPSc captured before carrying out the ELISA assay is preferable, since most of the high affinity anti-prion antibodies bind to the denatured form of PrP and many anti-prion antibodies that bind to PrP Denatured are known and commercially available. The dissociation and denaturing of the pathogenic prion can be achieved using high concentrations of chaotropic agents, for example, 3M to 6M of a guanidinium salt such as guanidinium thiocyanate or guanidinium hydrochloride. The chaotropic agent must be removed or diluted before the ELISA assay is carried out as it will interfere with the binding of the anti-prion antibodies used in the ELISA assay. This results in additional washing steps or generation of large sample volumes, both of which are undesirable for rapid high emission assays. The present inventors have discovered that in some embodiments a preferred alternative to the use of a chaotropic agent for the denaturing of the pathogenic prion protein, and the dissociation of the peptoid reagent, is the use of high or low pH. The pathogenic prion protein readily dissociates from the peptoid reagent and is denatured by adding components that increase the pH to more than 12 (e.g., NaOH) to less than 2 (e.g., H3P04). In addition, the pH can be easily readjusted to neutral by the addition of small volumes of suitable acid or base, thus allowing direct use in the ELISA assay without further washing and without significantly increasing sample volumes. The invention then provides a method for detecting the presence of a pathogenic prion in a sample, comprising: contacting the sample suspected of containing a pathogenic prion with a peptoid reagent that preferably interacts with the pathogenic form of the prion protein under that allow the binding of the peptoid reagent to the pathogenic prion protein, if present; remove the unbound sample material; dissociating the pathogenic prion from the peptoid reagent and detecting the presence of the dissociated pathogenic prion using a prion binding reagent. It will be apparent that if the particular prion binding reagent used binds to a denatured prion form that the pathogenic prion protein (captured) must be denatured before detection with the prion binding reagent. Preferably, the prion binding reagent is an anti-prion antibody. Antibodies, modified antibodies and other reagents, which bind prions, particularly PrPc or denatured PrP, have been described and some of these are commercially available (see, for example, anti-prion antibodies described in Peretz et al., 1997 J. Mol. Biol. 273: 614; Peretz et al., 2001 Nature 412: 739; Williamson et al., 1998 J. Virol. 72: 9413; Polymenidou et al., 2005 Lancet 4: 805; US Patent No. 6,765,088. these and others are commercially available, inter alia, from InPro Biotechnology, South San Francisco, CA, Cayman Chemicals, Ann Arbor MI, Prionics AG, Zurich, see also, WO 03/085086 for the description of modified antibodies). Suitable antibodies for use in the method include without limitation 3F4 (US 4,806,627), D18 (Peretz et al., J. Mol. Biol. 1997 273: 614), D13 (Peretz 1997, cited above), 6H4 (Liu et al., J. Histochem.

Cytochem. 2003 51: 1065), MAB5242 (Chemicon), 7D9 (Kascsak et al., 1987 J. Virol. 61: 3688), BDI115 (Biodesign International), SAF32, SAF53, SAF83, SAF84 (SAF antibodies available from SPI Bio, France) , 19B10 (WO2004 / 4033628), 7VC (WO2004 / 4033628), 12F10 (SPIBio), PRI308 (SPI Bio), 34C9 (Prionics AG), Fab HuM-P (Peretz et al., Nature 2001 412: 739), POM 1 to POM 19 (Polymenidou et al., 2005, cited above) Fab HuM-Rl (Peretz 1997, cited above) and Fab HuM-R72 (Peretz 1997, cited above). Other anti-prion antibodies can be easily generated by methods that are well known in the art. Preferred anti-prion antibodies will be those that bind to a denatured form of the pathogenic prion. Particularly preferred anti-prion antibodies will be those which recognize epitopes in the N-terminal region of the prion protein. Some anti-prion antibodies will be specific for prion protein of one or a limited number of animal species, others are capable of binding to prion proteins of many animal species. It will be apparent to select suitable anti-prion antibodies based on the samples that will be analyzed and the purpose of the test. In preferred embodiments, the peptoid reagent is provided on a solid support. The peptoid reagent can be provided on a solid support before contacting the sample or the peptide reagent can be adapted to bind solid support after contacting the sample and binding any pathogenic prion therein (eg using a biotinylated peptoid reagent and a solid support comprising an avidin or streptavidin). The invention then further provides a method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises: (a) providing a first peptoid reagent on a first solid support; (b) contacting the first solid support with a sample under conditions that allow pathogenic prion proteins, when present in a sample, to bind to the peptoid reagent to form a first complex; (c) removing unbound sample material; (d) dissociating the pathogenic prion proteins from the first complex and (e) detecting the pathogenic prion proteins by dissociating the prion binding reagent. The peptoid reagent may be any of those described herein, preferably, the peptoid reagent is derived from a sequence selected from the group consisting of SEQ ID NO: 229-241. The prion binding reagent is more described herein. Preferably, the prion binding reagent is an anti-prion antibody. The first solid support is preferably a magnetic sphere, most preferably a polystyrene / iron oxide sphere. Methods for attaching a peptoid reagent to a solid support are conventional in the art and are described on either side herein and include well-known methods for attaching proteins and peptides to various solid surfaces. The sample is contacted with the solid support comprising the peptoid reagent under conditions that allow the binding of any pathogenic prion protein in the sample to bind to the peptoid reagent, forming a first complex. These binding conditions are readily determined by one of ordinary skill in the art and are more fully described herein. Typically, the method is carried out in the wells of a microtiter plate or in small volume plastic tubes, but any convenient vessel will be suitable. The sample is generally a liquid sample or suspension and can be added to the reaction vessel before or after the peptoid reagent. Once the first complex is established, unbound sample material (ie, any component of the sample that has not been bound to the peptoid reagent), including any unbound pathogenic prion protein) can be removed by separating the solid support from the reaction solution (containing unbound sample materials) eg by centrifugation, precipitation, filtration, magnetic force, etc. The solid support with the first complex can optionally be subjected to one or more washing steps to remove any residual sample material before carrying out the following steps of the method. After removal of unbound sample materials and any optional washing, the bound pathogenic prion proteins dissociate from the first complex. This dissociation can be achieved in a number of ways. In one embodiment, a chaotropic agent, preferably a guanidinium compound, for example guanidinium thiocyanate or guanidinium hydrochloride, are added at a concentration of between 3M and 6M. The addition of the chaotropic agent under these conditions causes the pathogenic prion protein to dissociate from the peptoid reagent and also cause the pathogenic prion protein to denature. In another embodiment, dissociation is achieved either by raising the pH to 12 or more ("high pH") or lowering the pH to 2 or less ("low pH"). Exposure of the first complex either at high or low pH results in the dissociation of the pathogenic prion protein from the peptoid reagent and causes the pathogenic prion protein to denature. In this embodiment, exposure of the first complex at high pH is preferred. A pH of between 12.0 and 13.0 is generally sufficient; preferably a pH of between 12.5 and 13.0 is used; most preferably a pH of 12.7 to 12.9; more preferably a pH of 12.9. Alternatively, exposure of the first complex at a low pH can be used to dissociate and denature the pathogenic prion protein of the peptoid reagent. For this alternative, a pH between 1.0 and 2.0 is sufficient. The exposure of the first complex either at a high pH or at a low pH is carried out only for a short time, for example 60 minutes, preferably for no more than 15 minutes, most preferably for no more than 10 minutes. Longer exposures than this may result in a significant deterioration of the structure of the pathogenic prion protein in such a way that the epitopes recognized by the anti-prion antibodies used in the detection steps are destroyed. After exposure for a sufficient time to dissociate the pathogenic prion protein, the pH can easily be re-adjusted neutral (ie, pH between about 7.0 and 7.5) by the addition of either an acid reagent (if conditions are used). high pH dissociation) or a basic reagent (if low pH dissociation conditions are used). One of ordinary skill in the art can easily determine the protocols and suitable examples as described herein. In general, to carry out a dissociation condition at high pH, the addition of NaOH at a concentration of about 0.05 N to about 0.2 N is sufficient. Preferably, NaOH is added at a concentration between 0.05 N to 0.15 N; most preferably, 0.1 N NaOH is used. Once the dissociation of the pathogenic prion from the peptoid reagent is achieved, the pH can be re-adjusted to neutral (i.e., between about 7.0 and 7.5) by the addition of suitable amounts of a acid solution, for example, phosphoric acid, sodium phosphate monobasic. In general, to bring a dissociation condition to low pH, the addition of H3P04 at a concentration of about 0.2 M to about 0.7 M is sufficient. Preferably, H3P04 is added at a concentration between 0.3 M and 0.6 M; most preferably 0.5M H3P04 is used. Once the dissociation of the pathogenic prion from the peptoid reagent is achieved, the pH can be re-adjusted to neutral (i.e., between about 7.0 and 7.5) by the addition of adequate amounts of a solution basic, for example, NaOH or KOH. The dissociated pathogenic prion protein is then separated from the solid support comprising peptoid reagent. This separation can be achieved in a manner similar to the removal of the bound sample materials described above except that the portion containing the unbound materials (now the dissociated pathogenic prion protein) is retained and the portion of the solid support material is discarded. The dissociated pathogenic prion protein can be detected using prion binding reagents. A number of these prion binding agents are known and described herein. Preferred prion binding reagents for the detection of the dissociated pathogenic prion protein are anti-prion antibodies. A number of anti-prion antibodies have been described and many are commercially available, for example, Fab D18 (Peretz et al (2001) Na ture 412: 739-743), 3F4 (available from Sigma Chemical St. Louis MO; see also , U.S. Patent No. 4,806,627), SAF-32 (Cayman Chemical, Ann Arbor MI), 6H4 (PrionicAG, Switzerland, see also U.S. Patent No. 6,765,088), POMS 1 to 19 (Polymenidou et al, The Lancet 2005 4: 805) and others described above and well known in the art. The dissociated pathogenic prion proteins can be detected in an ELISA-type assay, either as an indirect ELISA or an ELISA-type sandwich of antibodies, which are described more fully below. Although the term "ELISA" is used to describe detection with anti-prion antibodies, the assay is not limited to those in which the antibody is "enzyme bound". The detection antibodies can be labeled with any of the detectable labels described herein well known in the immunoassay art. In one embodiment of the method, the dissociated pathogenic prion protein is coated passively on the surface of a second solid support. The methods for this passive coating are well known and are typically carried out in 100 mM NaHCO3 at pH 8 for several hours at about 37 ° C or overnight at 4 ° C. Other pH regulators of coating are well known ( for example, 50 mM carbonate pH 9.6, 10 mM Tris pH 8 or 10 mM PBS pH 7.2). The second solid support can be any of the solid supports described herein well known in the art; preferably the second solid support is a microtiter plate, for example, a 96-well polystyrene plate. When the dissociation has been carried out using a high concentration of chaotropic agent, the concentration of the chaotropic agent will be reduced by dilution at least about 2 times before coating on the second solid support. When dissociation has been carried out using a high or low pH, followed by neutralization, the dissociated pathogenic prion protein can be used to coat without any further dilution. Once the dissociated pathogenic prion protein is coated on the second solid support, the support can be washed to remove any component that is not adhered to the solid support. The anti-prion antibodies are added under conditions that allow the binding of the antibodies to the prion protein coated on the second solid support. If the dissociated pathogenic prion protein has been denatured before coating on the second solid support, the antibodies used will be those that bind to the denatured form of the prion protein. These antibodies include those that are well known (such as those described herein) as well as antibodies that are generated by well known methods, for example, using rPrP, PrPc or fragments thereof, to develop an immune reaction in mice, rabbits, rats, etc. (See, U.S. Patents Nos. 4,806,627, 6,165,784, 6,528,269, 6,379,905; 6,261,790; 6,765,088; 5,846,533; EP891552B1 and EP 909388B1). Anti-prion antibodies that recognize epitopes at the N-terminus of the prion protein are particularly preferred, for example, antibodies that recognize epitopes within the region of residues 23-90. Thus, the invention in one embodiment provides a method for detecting the presence of a pathogenic prion in a sample, comprising: (a) providing a first peptoid reagent on a first solid support; (b) contacting the first peptoid reagent with a sample under conditions that allow the pathogenic prion proteins, when present in the sample, to bind to the peptoid reagent to form a first complex; (c) removing unbound sample material; (d) dissociating the pathogenic prion proteins from the first complex; (e) separating dissociated pathogenic prion proteins from the first solid support; (f) contacting the dissociated pathogenic prion proteins with a second solid support under conditions that allow the dissociated prion protein to adhere to the second solid support and (g) detect the pathogenic prion proteins adhered to the second solid support using a reagent union to prions. In this embodiment, the first solid support is preferably a magnetic sphere; the second solid support is preferably a microtiter plate; the prion binding reagent is preferably an anti-prion antibody, in particular 3F4, 6H4, SAF32 or one or more of the POM antibodies described in Polymenidou, cited above. The prion binding reagent is detectably labeled. In another embodiment of the method, the dissociated pathogenic prion proteins are detected using a sandwich ELISA of antibodies. In this embodiment, the dissociated prion protein is "recaptured" on a second solid support comprising a first anti-prion antibody. The second solid support with the recaptured prion protein is optionally washed to remove any unbound material, and then contacted with a second anti-prion antibody under conditions that allow the second anti-prion antibody to bind to the recaptured prion protein. The first and second anti-prion antibodies will typically be different antibodies and will preferably recognize different epitopes in the prion protein. For example, the first anti-prion antibody will recognize an epitope at the N-terminus of the prion protein and the second anti-prion antibody will recognize an epitope at another end other than the N-terminus, or vice versa. The first antibody can be, for example, SAF32 which recognizes an epitope in the region of the repeat (residues 23-90) and the second antibody can be 3F4, which recognizes an epitope at residues 109-112; as an alternative,. the first antibody can be 3F4 and the second antibody can be SAF32. Other combinations of first and second antibody can be easily selected. In this embodiment, the second anti-prion antibody, but not the first anti-prion antibody, will be labeled in detectable form. When the dissociation of the pathogenic prion protein from the peptoid reagent is carried out using a chaotropic agent, the chaotropic agent must be removed or diluted at least 15 times before carrying out the detection assay. When the dissociation is carried out using a high or low pH and neutralization, the dissociated prion can be used without further dilution. When the dissociated pathogenic prion protein is denatured before carrying out the detection, the first and second antibodies will bind both to the denatured prion protein. The invention then provides a method for detecting the presence of a pathogenic prion in a sample, comprising: (a) providing a first peptoid reagent as described herein on a first solid support; (b) contacting the first peptoid reagent with a sample under conditions that allow the pathogenic prion proteins, when present in the sample, to bind to the peptoid reagent to form a first complex; (c) removing unbound sample material; (d) dissociating the pathogenic prion proteins from the first complex, whereby the pathogenic prion protein is denatured; (e) separating denatured and dissociated pathogenic prion proteins from the first solid support; (f) contacting the denatured and dissociated pathogenic prion proteins with a second solid support, wherein the second solid support comprises a first anti-prion antibody, under conditions that allow the dissociated prion protein to bind to the first anti-prion antibody and (g) detecting the bound prion proteins on the second solid support with the second anti-prion antibody. In this embodiment, the first solid support is preferably a magnetic sphere; the second solid support is preferably a microtiter plate or a magnetic sphere; the first and second anti-prion antibodies are preferably different antibodies; the first and second antibodies bind preferentially to denatured prion protein; Preferably, at least one of the first and second anti-prion antibodies recognizes an epitope in the N-terminal region of the prion protein. In some embodiments, the second anti-prion antibody is detectably labeled; in additional embodiments, the second anti-prion antibody is labeled with enzymes. Any of the detection methods for a pathogenic prion described hereinabove can be used in a method for diagnosing a prion-related disease.

Diagnosis and treatment The invention further provides methods for treating or preventing a prion-related disease comprising administering to an animal one or more peptoid reagents, or compositions thereof, as described herein. The invention also provides methods for determining an infection level of prion-related disease in an animal, which can be used to make a diagnosis and evaluate the need for treatment or prevention. If treatment or prevention is necessary, it may or may not be for prion-related disease. That is, if it is determined that no prion infection is present, treatment or prevention may be necessary for a disease, disorder, condition or symptom unrelated to prions. This treatment can be, for example, a conventional medicament. The invention also provides methods for identifying the location of the prion-related infection. The term "treatment" or "treating", as used herein, means curing, reducing or reversing the progress of a disease or disorder, or decreasing or reversing one or more symptoms or side effects of this disease or disorder. The term "administer" as used herein means administering directly to the peptoid reagent or a composition thereof, which will provide a therapeutically effective amount of the peptoid reagent in the recipient animal. As used herein, the phrase "therapeutically effective amount" refers to the amount of active peptoid reagent, or composition, that develops the biological or medicinal response that is being sought in a system, tissue, animal, individual or human by a researcher, veterinarian, medical doctor or other clinician, which includes one or more of the following: (1) prevent the disease; for example, preventing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but who has not yet experienced or presented the pathology or symptomatology of the disease; (2) inhibiting the disease, for example, inhibiting a disease, condition or disorder in an individual who is experiencing or presenting the pathology or symptomatology of the disease, condition or disorder and (3) decreasing the disease; for example, decreasing a disease, condition or disorder of an individual who is experiencing or presenting the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology) such as by reducing the severity of the disease ). In some embodiments, the method comprises obtaining a sample of the animal; detecting a presence of a pathogenic prion according to any of the detection methods of the invention and determining the level of infection of prion disease from the presence or absence of the detected pathogenic prion. In some embodiments, a method for determining a location of a prion-related disease infection in an animal is provided, wherein the method comprises administering to the peptoid reactive animal of the invention, or composition thereof, wherein the peptoid reagent is linked. to an imaging agent and detecting the imaging agent, thereby locating the prion-related disease infection in the animal. In some embodiments of a method for treating or preventing a prion-related disease in the animal, the method comprises determining the presence of one or more pathogenic prions in the animal according to a detection method of the invention; then, administering one or more peptoid reagents of the invention, or compositions comprising the same, to the animal following a determination that one or more pathogenic prions are present; or administering one or more conventional drugs to the animal after a determination that one or more pathogenic prions are not present. In some modalities, the method comprises administering one or more conventional medicaments to the animal after determination that infection of the prion-related disease is present. In some embodiments, the sample to be tested comprises organic matter, cells, whole blood, a fraction of blood, a blood component, plasma, a platelet, serum, cerebrospinal fluid (CSF), brain tissue, nervous system tissue, muscle tissue, muscle and fat tissue, bone marrow, urine, tears or non-nervous system tissue. In some embodiments of the method for treating or preventing prion-related diseases in an animal, the method comprises administering to the animal a first dose comprising a peptoid reagent of the invention, or composition comprising the same, and administering to the animal a second dose that it comprises a peptoid reagent of the invention, or composition comprising the same, in an amount sufficient to induce an immune response in the animal. An "immune response", as used herein, is the development in the animal of a humoral and / or cellular immune response to a peptoid reagent such as when the peptoid reagent is present in a vaccine. Thus, the immune response generally results in the development in the animal of a secretory, cellular and / or antibody-mediated immune response. Usually, this response includes, but is not limited to, one or more of the following effects: the production of antibodies from any of the immunological classes, such as immunoglobulins A, D, E, G or M, lymphocyte proliferation B and T, the provision of activation signals, growth and differentiation to immune cells and the expansion of T helper cells, suppressor T cells and / or cytotoxic T cells. The amount of antibodies produced will vary depending on several factors including the animal involved, the number of doses of the composition administered, the presence of an adjuvant, etc. Some peptoid reagent compositions of the invention further comprise an adjuvant. In some of these embodiments, the method for treating or preventing a prion-related disease in an animal, the first dose and / or the second dose comprises at least one adjuvant. In some of these embodiments, both the first and second doses comprise an adjuvant. Non-limiting examples of adjuvants useful in the doses and compositions of the invention include those in WO05 / 016127, incorporated herein in their entirety. In some embodiments of the method for treating or preventing a prion-related disease in an animal, the animal has been diagnosed as infected with a pathogenic prion. In some embodiments, the animal has been in close proximity to a second animal that has been diagnosed as infected as a pathogenic prion. "Close proximity" means that the animal is and is in the same herd or community of animals, in the same farm, ranch or similar, or that is transported, processed, etc., with the animal diagnosed. In some embodiments, the animal is a member of the family of a second animal that has been diagnosed as infected with a pathogenic prion. In some embodiments, the animal exhibits symptoms associated with an animal infected with prions. In some modalities, the animal is at risk of a prion-related modality. An "at-risk" animal may be one that has a prediposition, genetically or otherwise, for example, environmentally, towards development, contraction, reception, being exposed to or the like, to a disease related to prions. An environmental predisposition includes, for example, an animal in a herd or community that is living in an area, geographically or physically, where there has been exposure to a prion-related disease. In some embodiments, the animal at risk is a progeny of an animal infected or suspected of being infected with a pathogenic prion. In some modalities, the animal at risk has ingested biological materials derived from a second animal, where the second animal is infected with or at risk of a disease related to prions. A composition comprising the first dose may be the same or different as that of the second dose. In some embodiments, the composition of the second dose is the same as that of the first dose. In some embodiments, the compositions of the first and second doses are different. In some embodiments, the method further comprises administering a conventional medicament. In some embodiments, the conventional medicament comprises antibodies, oligonucleotides, organic compounds or peptidomimetics. In some embodiments, the conventional medicament is an antigen or immunoregulatory agent such as immunoglobulins, coticins, lymphokines and chemokines, including but not limited to interieukin 2 (IL-2), modified IL-2 (cysl25-serl25), colony stimulating factor. of macrophages or granulocytes (GM-CSF), interieucine 12 (IL-12), alpha- or gamma-interferon, chemokine IP-10 and β chemokines such as RANTES, MlPI-a, and MlPI-β. The animal in any of the methods of treatment and prevention of the invention comprises human or non-human. For non-human animals, the animal can be wild, that is, not domesticated, for example, deer, elk, antelope, bear, mountain goat, llama, bison, horses, mules and donkeys, large cats such as panthers, mountain lions , puma, tigers, lions and cheetahs, and smaller mammals, for example, rabbits, prairie dogs, raccoons, skunks and the like, or birds; or domesticated, including, for example, domesticated pets, for example, cats, dogs, ferrets, rabbits, rats or mice, farm animals and livestock, for example, cows, cattle, sheep, pigs, goats, horses, mules and donkeys , or birds, for example, chickens, chickens, ducks, geese, turkeys and other gallinaceous birds and laboratory animals, that is, non-human primates such as apes, monkeys and lemurs, and rodents such as mice, rats, hamsters and guinea pigs of Indians Animals suitable for use with the invention can be of any age, including both adults and newborns. In some modalities, the animal is a mammal. In some modalities, the mammal is a human. In some modalities, the mammal is not a human. In some embodiments, the composition is administered as described hereinabove. In some embodiments, the mammal comprises a cat, dog, ferret, rabbit, rat, mouse, cow, ox, sheep, lamb, pig, goat, horse, mule, donkey, deer, elk, bison, bear, cougar, lion mountain, ape, monkey, lemur, hamster or guinea pig. In some embodiments the mammal comprises cow, ox, deer, sheep, lamb, pig or goat. In some embodiments, the composition is administered intramuscularly, intramucosally, intranasally, subcutaneously, intradermally, transdermally, intravaginally, intrarectally, orally or intravenously.

Isolation, reduction and elimination The present invention also provides methods for isolating a pathogenic prion from a sample or reducing the amount of a pathogenic prion in the sample. The method for isolating a pathogenic prion from a sample comprises providing a solid support comprising a peptoid reagent of the invention; contacting the solid support with the sample under conditions that allow the binding of the pathogenic prion, if present in the sample, to the peptoid reagent to form a complex, and then remove unbound sample, thereby providing an isolated pathogenic prion. In some embodiments, the method further comprises dissociating the pathogenic prion from the complex. The method for reducing the amount of the pathogenic prion in a sample comprises providing a solid support comprising a peptoid reagent of the invention; then, contacting the solid support with the sample under conditions that allow binding of the pathogenic prion, if the sample is present to the peptoid reagent of the support and recover unbound sample, thereby providing a sample with a reduced amount of the pathogenic prion . In some embodiments, the amount of the pathogenic prion is reduced below a detectable level. In some embodiments, the amount of the pathogenic prion is reduced by about 80 to 100, about 85 to 100, about 90 to 100 or about 95 to 100%. The invention further provides a method for preparing a blood source that is substantially free of a pathogenic prion, wherein the blood source comprises blood samples taken such as those from a blood bank or those taken from a patient prior to surgery, for example, a self-originated transfusion before surgery. The blood supply may include, for example, without limitation, whole blood, plasma, platelets or serum. In some embodiments, the method comprises detecting the presence or absence of a pathogenic prion in a plurality of samples according to a detection method of the invention, and combining the samples in which the pathogenic prion is not detected, thus providing the supply of blood that is substantially free of the pathogenic prion. In some embodiments, the detection method of the invention comprises allowing a peptoid reagent to bind to the pathogenic prion, if present, to form a complex, and detect the presence of the pathogenic prion in the sample by binding it to the peptoid reagent. In some embodiments, the binding of the pathogenic prion to the peptoid reagent can be detected upon detection of complex formation, the formation of the complex being indicative of the presence of the pathogenic prion. In some embodiments, the complex comprising the peptoid reagent and the pathogenic prion protein is separated from the rest of the sample (i.e., the unbound sample) before detection. In some embodiments, complex formation can be detected by detecting the pathogenic prion in the complex or by dissociating the complex (after separation of the unbound sample) and detecting the dissociated pathogenic prion. The invention also provides a method for preparing a food source such as a meat source (e.g., muscle and fat tissue (ie, meat) from cattle, sheep or pigs, eg, beef, lamb, mutton or swine. for human or animal consumption) that is substantially free of pathogenic prions. In some embodiments, the method comprises detecting the presence or absence of pathogenic prion in a plurality of samples according to a detection method of the invention, and combining the samples which the pathogenic prion is not detected, thus providing the food supply. which is substantially free of the pathogenic prion. In some embodiments, the food source is collected from a living or once live organism that will enter the food or feed supply intended to enter the food supply. In some modalities, the detection method of the invention comprises allowing a peptoid reagent to bind to the pathogenic prion, if present, to form a complex, and detect the presence of the pathogenic prion in the peptoid reagent binding sample. In some embodiments, the binding of the pathogenic prion to the peptoid reagent can be detected by detecting the presence of the pathogenic prion, the formation of the complex being indicative of the presence of the pathogenic prion. In some embodiments, the complex comprising the peptoid reagent and the pathogenic prion protein is separated from the rest of the sample (i.e., the unbound sample) before detection. In some embodiments, complex formation can be detected by detecting the pathogenic prion in the complex or by dissociating the complex (after separation of the unbound sample) and detecting the dissociated pathogenic prion.

Design The invention further provides a method for designing a peptoid reagent of the invention. As a starting point, the peptoid reagent can be designed based on the sequences of certain peptide fragments of a prion protein (eg, fragments of peptides having SEQ ID Nos: 12-228) by making amino acid residue replacement in the sequence of the peptide fragment with N-substituted glycines, synthesis of the modified peptide using methods described in US Pat. Nos. 5,811,387, 5,831,005, 5,877,278, 5,977,301 and 6,033,631, as well as Simón et al. (1992) Proc. Na ti. Acad. Sci. USA 89: 9367, publications which are incorporated herein by reference in their entirety, by testing the modified peptide for binding to pathogenic prion proteins by methods described herein. Additional replacements can be made according to the replacement scheme below until an adequate peptoid reagent is achieved. In addition, the design of the peptoid reagent may comprise aspects of the Solid Phase Submonomeric Syn thesis Protocol for Peptoides described in Example 5, below.

In some embodiments, the method for making a peptoid reagent of the invention comprises: a) providing a peptide fragment of a prion protein; replacing a first amino acid of a peptide fragment with an N-substituted glycine by means of the following replacement: i) Ala, Gly, Lie, Leu, Pro and Val are replaced by N- (alkyl) glycine, N- (aralkyl) glycine or N- (heteroarylalkyl) glycine; ii) Asp, Asn, Cys, Gln, Glu, Met, Ser and Thr are replaced by N- (hydroxyalkyl) glycine, N- (alkoxy) glycine, N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine; iii) Phe, Trp and Tyr are replaced by N- (aralkyl) glycine, N- (heteroarylalkyl) glycine, N- (hydroxyalkyl) glycine or N- (alkoxyalkyl) glycine and iv) Arg, His and Lys are replaced by N- (aminoalkyl) glycine or N- (guanidinoalkyl) glycine; b) replacing a second amino acid in the peptide fragment with an N-substituted glycine according to step a); c) replacing a third amino acid of the peptide fragment with an N-substituted glycine according to step a) and d) optionally, repeating step c) 1-27 times, in this manner, providing a designed peptoid reagent comprising 3 to 30 N-substituted glycines and synthesizing the peptoid reagent designed. In some embodiments of the above method, the peptide fragment comprises a peptide having a sequence selected from the group consisting of SEQ ID NOs: 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 , 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 , 49, 50, 51, 52, 53; 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132 133, 134, 135, 135, 137, 138, 139, 140, 141, 142, 143, 144 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180 181, 182, 183, 184, 185, 18 6, 187, 188, 189, 190, 191, 192 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227 and 228. In some embodiments of the above method, the peptide fragment comprises a peptide having a sequence selected from the group consisting of SEQ ID NOs: 66, 67, 68, 72, 81 , 96, 97, 98, 107, 108, 109, 14, 35, 36, 37, 40, 50, 5, 77, 89, 100, 101, 110, 56, 57, 65, 82, 84, 111, 112 , 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156 , 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 278, 279, 180, 181 , 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206 , 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, and 228. In some embodiments of the above method, the fragment The peptide comprises a peptide having a sequence selected from the group consisting of SEQ ID NOs: 12, 14, 150, 51, 52, 68, 72, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 135, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180 , 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205 , 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218 and 219. In some embodiments of the above method, the peptide fragment comprises a peptide having a sequence selected from the group of consists of SEQ ID NOs: 14, 50, 51, 52, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218 and 219. In some embodiments of the above method, the peptide fragment comprises a peptide. having a sequence selected from the group consisting of SEQ ID NOs: 12, 68, 72, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 135, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159 and 160. In some embodiments of the design method for the peptoid reagent, the peptide fragment comprises a peptide having a sequence selected from the group consisting of SEQ ID NOs: 12, 14, 50 , 51, 52, 67, 68, 72 and 109. In some embodiments, the peptide fragment comprises a peptide having a sequence of SEQ ID NO: 14 or 68. In some embodiments, the method further comprises adding to the peptoid reagent a selected conjugated portion of an effector molecule, a substrate, or a label, each optionally linked to the peptoid reagent through a linker portion. In some embodiments, a conjugated portion comprises biotin. In some embodiments, the conjugated portion comprises a mercapto group.

OTHER USES The invention also provides a solid support comprising at least one peptoid reagent of the invention. The solid support can be as previously described herein. The invention further provides a kit for detecting the presence of a pathogenic prion in a sample. In some embodiments, the kit comprises a peptoid reagent of the invention. In some embodiments, the kit comprises a solid support comprising a peptoid reagent of the invention. In some embodiments, the kit comprises a solid support comprising a peptoid reagent of the invention and a reagent. The reagent may be, for example and without limitation, a detection reagent such as a detectably labeled antibody, chromophore, chromogen, a prion binding reagent such as anti-prion antibodies, hybrid polypeptides grafted to motifs, cationic polymers or anionic, propagation catalysts and a plasminogen or a pH regulator. In some embodiments, the kit comprises two or more peptoid reagents of the invention. In some kit modalities, positive and / or negative controls are optionally included. In order that the invention described herein may be understood more efficiently, examples are given below. It should be understood that these examples are for illustrative purposes only and should not be construed as limiting the invention in any way.

EXAMPLES Example 1 Peptoid Region Sequences Table 1 lists exemplary peptoid regions (amino-to-carboxy-directed) suitable for preparing peptoid reagents of the present invention. Table 2 provides a key for the abbreviations used in Table 1. Table 3 provides the relevant structures of each of the sequences. The peptoid reagents containing the sequences of Table 1 were tested for preferential binding to PrPSc, according to the assays described herein. The preparations of the specific reagents are described below.

Table 1 Representative peptoid regions for peptoid reagents of the invention Table 2 List of abbreviations for table 1 Table 3 Relevant structures of peptoid regions of table 1 Example 2 Peptoid Reagents The following peptoid reagents were prepared using synthetic methods for the preparation of peptoid molecules containing N-substituted glycine residues such as the procedures described in the U.S. Patents. Nos: 5,811,387, 5,831,005, 5,877,278, 5,977,301 and 6,033,631, as well as Simón et al. (1992) Proc. Na ti. Acad. Sci. USA 89: 9367, each of which is incorporated herein by reference in its entirety, and using the protocol described in example 5. Each of the following reagents was tested for binding affinity for a prion protein of according to the assays described herein.

Peptoid reagent I The following peptoid reagent comprises SEQ ID NO: 229 Calculated mass: 1054.42; Observed mass: 1054.2. All observed mass measurements were measured in a Waters system (Milford, MA) Micromass ZQ LC / MS System.

Peptoid reagent II The following peptoid reagent comprises SEQ ID NO: 230 Calculated mass: 1290.70; Observed Mass: 1290.8 Peptoid III Reagent The following peptoid reagent comprises SEQ ID NO: 231 Calculated mass: 1861.30; Observed Mass: 1861.6.

Peptoid IV reagent The following peptoid reagent comprises SEQ ID NO: 232.

P peptoid reagent The following peptoid reagent comprises SEQ ID NO: 233, Peptoid VI Reagent The following peptoid reagent comprises SEQ ID NO: 234.

Calculated mass: 1956.49; Observed Mass: 1956.2.

Peptide reagent VII The following peptoid reagent comprises SEQ ID NO: 235 Calculated mass: 1896.39; Observed mass 1896.4.

Peptoide VIII reagent The following peptoid reagent comprises SEQ ID NO: Calculated Mass: 1732.8; Observed mass 1732.4.

Peptoid reagent IX The following peptoid reagent comprises SEQ ID NO: 237 Calculated mass: 1248.65; Observed Mass: 1248.4.

Peptoide Reagent X The following peptoid reagent comprises SEQ ID NO: 238.

Calculated mass: 1248.65; Observed Mass: 1248.4.

Peptoid reagents Xla and Xlb The following peptoid reagents Xla and Xib, comprise SEQ ID NO: 239.

Xla Xlb. Xla: Calculated mass: 1304.76; Observed Mass 1304. 6, Xlb: Calculated mass: 1166.59; Observed Mass: 1166 2 Xlla and Xllb peptoid reagents The following peptoid reagents of the formulas Xlla and Xllb comprise SEQ ID NO: 240. xpb.

Xlla: Calculated mass: 1276.71; Observed Mass: 1276.6, Peptoid Reagent XIII The following peptoid reagent comprises SEQ ID NO: 241.

Calculated mass: 1256.58; Observed Mass: 1256.6.

EXAMPLE 3 BINDING TESTS Descending Pull Test The peptoid reagents of Example 2 were tested for their ability to specifically bind to pathogenic prion proteins using a tensile tensile test of magnetic spheres. For this assay, peptoid reagents were fixed to magnetic spheres in one of two ways: 1) the peptoid reagents were labeled with biotin, which allowed fixation to streptavidin-coated magnetic spheres or 2) the peptoids were covalently linked to magnetic spheres through of a propionic thiol acid. The mode of attachment of the peptoid reagent to the spheres had little effect on the binding activity of the peptoid reagent; however, when the peptoid reagents were covalently fixed to the spheres, less background interference from plasma samples used as a diluent was observed. The magnetic spheres were obtained from Dynal (Brown Deer, Wl). Typically, ten microliters (10 μl) of Streptavidin M-280 Dynabeads® (cat # 112.05) were used for the individual downward pull reaction using biotinylated peptoid reagent. Human brain homogenates (10% w / v in sucrose 0.25 M) of deceased CJD patients and healthy deceased individuals (ie, without CJD) were obtained from the National Institute for Biological Standards and Controls (NIBSC), Blanche Lane South Mimms , Pottersbar, United Kingdom. For most of the experiments described herein, samples from 3 patients with CJD (one patient nvCJD and two patients sCJD) were combined and tests were performed on the combined brain homogenate samples. Aliquots of 200 μl were diluted 1: 1, vol: vol, in pH regulator TBS (50 mM Tris-HCl pH 7.5 and 37.5 mM NaCl) containing 1% Triton XlOO and 10% Tween-20 and the sample was sonified for several repetitions of several seconds each. Aliquots of brain homogenate were maintained at -70 ° C. To evaluate the binding of the peptoid reagent to PrPSc, CJD brain homogenates were splashed into human plasma from a healthy individual. In general two negative control samples were used: 1) normal human plasma and 2) normal human plasma splashed with normal human brain homogenate (without CJD). The standard test concentration of human plasma varied from 0 to 80% of the total sample volume. In a typical protocol, for a downward tensile test (final 100 μl in a 96-well microtitre plate well), 10 μl of Streptavidin M-280 Dynabeads® (cat # 112.05) are used. The appropriate amount of beads is washed once before using with TBS containing 1% Tween-20 and 1% Triton X-100 (TBSTT). The pellets of spheres are resuspended in 10 times the original volume, that is, 100 μl with TBSTT. Subsequently, 0.1 μl of biotinylated peptoid reagent supply solution (10 mM in H20) is added to the solution of spheres, mixed at room temperature, 750 rpm (Eppendorf, Thermomixer R) for 1 hour or 30 minutes 750 rpm at 37 ° C. Supernatants containing unbound peptoids are discarded and the spheres are washed three times using TBS and Tween-20, 0.05% (TBST) using a magnet apparatus that holds T-spheres at the bottom of the tube. At this stage, streptavidin magnetic spheres coated with peptoid reagent are obtained. Then, the magnetic spheres coated with peptoids (representing the original μl starting volume) are mixed with various concentrations of CJD 10% brain homogenate in the presence of plasma (final concentration of 0-80%), lx of TBS, 1% of Triton XlOO and 1% of Tween-20 to a final volume of 100 μl. A typical reaction volume is 100 μl in 96-well plate well. The plate is shaken at 750 rpm (Eppendorf, Thermomixer R) for 1 hour at 37 ° C. The spheres are washed to remove unbound protein, four times with TBS solution containing 0.05% Tween-20, using Magna ELx405 plate washer (Bio-Tek Instruments, Inc., Winooski, VT). This microtitre plate washer is specifically designed for applications using magnetic sphere technology. A second carrier places the magnetic plate near the bottom of the microplate, securing the magnetic spheres during the critical suction cycles.

ELISA After the final wash of the Descent Traction test, PrPSc is eluted from the spheres, denatured and detected with monoclonal anti-prion antibodies (mAbs) in ELISA format (enzyme-linked immunosorbent assay). In an assay format (an indirect ELISA), the anti-prion mAb detection, which is proportional to the amount bound to PrP? C, is achieved with secondary polyclonal antibody that recognizes the primary monoclonal. The secondary antibody is conjugated to the enzyme alkaline phosphatase. When incubated with chemiluminescence substrate, the enzyme degrades a chemical compound resulting in the emission of light that is measured by a standard microplate chemiluminescence reader. The measured units are defined as relative light units (RLU). In the second format (a direct ELISA), the detection is carried out using monoclonal anti-prion antibodies (mAb) which are conjugated to alkaline phosphatase, thus no secondary antibody is required. The equal chemiluminescence substrate (Lumi-Phos Plus From Lumingen, Inc.) is used for both formats. Sandwich ELISA formats can also be used, as described herein. The ELISA can be carried out in any of a number of formats, for example in plates, in spheres, on magnetic particles. The eluted and denatured prion can be passively coated onto the solid support or can be joined in an antibody-antigen sandwich-like arrangement, the anti-prion antibody being coated on the solid support.

Results The results of the binding assays by ELISA are summarized below. Most representative peptoid reagents of the invention tested have similar binding efficiency to that of the peptide of SEQ ID NO: 68. In previous studies, the peptide of SEQ ID NO: 68 had adequate binding efficiency for prion proteins (see, for example, U.S. Patent Application Serial No. 11 / 056,950, filed February 11, 2005) and thus, was used as a reference value to measure the binding efficiencies of the peptoid reagents of the invention. The data in Table 4 show the signals obtained in descendent e / ELI SA tensile tests using various peptoid reagents compared to a peptide reagent (SEQ ID NO: 68, described in the co-owned EUA applications Serial No. 10 / 917,646, filed August 13, 2004, US Serial No. 11 / 056,950, filed on February 11, 2005 and international application PCT / US200 / 026363, filed August 13, 2004). The signals from a 1 ul sample of a 10% CJD brain homogenate or from a 1 ul sample of a 10% normal brain homogenate, both in 70% plasma, are shown. The column to the far right reports the experimental average of the peptoid reagent assays as a percentage of the experimental average of the peptide assay SEQ ID NO: 68.

Table 4 Percentage of union of representative peptoid reagents in 70% human plasma compared to the peptide of SEQ ID NO: 68 * SD = standard deviation, Table 5 Percent binding of representative peptoid reagents in 70% human plasma compared to the peptide of SEQ ID NO: 68 SD standard deviation.

Table 6 Percent binding of representative peptoid reagents in 20% human plasma compared to peptide of SEQ ID NO: 68 * SD = standard deviation. As shown in Tables 4 and 5, in 70% plasma, many of the representative peptoid reagents tested have a higher binding affinity than that of the reference peptide SEQ ID NO. 68, and commonly around 10 to 25% more. Tables 4 and 5 also show the specificity of the peptoid reagents for the pathogenic form of the prion protein (only the non-pathogenic form of the prion protein is expected to be present in normal brain homogenates). Table 6 shows the results of the descending tensile / ELISA tests with peptoid reagents in CJD brain homogenate diluted in 20% human plasma.

Table 7 Percent binding of the representative peptoid reagent bound directly to magnetic beads in 70% human plasma compared to the peptide of SEQ ID NO: 68 * SD = standard deviation. The peptoid reagent comprising SEQ ID NO: 240 (Xllb) was covalently attached to magnetic beads, the peptides comprising SEQ ID NO: 68 were also covalently attached to magnetic beads. The reagents that were covalently linked were used in a down-traction / ELISA reaction as described above for the biotinylated peptoid reagents and peptides bound to the SA spheres. The covalent binding of the reagents to the spheres did not significantly affect the ability of the spheres to interact preferentially with the pathogenic prions.

Specificity of Reagents for Pathogenic Form As shown in Tables 4 and 5 above, peptoid reagents can lower PrP? C which is present in human brain homogenates of CJD patients but do not pull any of the PrPc present in human plasma or in the homogenate of normal human brain witness. Additional experiments comparing the binding of peptoid reagents to CJD brain homogenates and normal homogenates (ie, without CJD) are shown below.

Table 8 Binding of peptoid reagents to 2 microliters of 10% normal homogenate or brain CJD in 70% human plasma Table 9 Union of peptoid reagents at 0.1 microliter of 10% CJD brain homogenate or 1 microliter of 10% normal human brain homogenate in 70% human plasma The experiments in Table 10 were carried out in a sample of human vCJD brain homogenate instead of a mixture of vCJD and sCJD BH.

Table 10 Peptide reagent binding 240 (Xllb) covalently linked to magnetic beads to normal brain homogenate or vCJD in 70% human plasma Table 11 Union of peptoid reagent 240 (X lb) covalently fixed to magnetic spheres In the course of these experiments, it was observed that certain samples of human plasma apparently contained certain material that interfered with the binding reaction and resulted in lower signals when those plasmas were used as the diluents. Experiments were carried out in comparison with peptoid reagents that were covalently bound to the magnetic spheres and the same peptoid reagents bound to the magnetic spheres by binding to biotin-streptavidin (Table 12 against Table 13). The covalently coupled peptoid reagents were much less sensitive to variations in the plasma samples used as diluent.

Table 12 Top-down tensile tests using representative biotinylated peptoid reagent bound to streptavidin magnetic spheres in various human plasmas * SD = Standard deviation.

Table 13 Top-down tensile tests using representative peptoid reagent attached directly to magnetic spheres in various human plasmas * SD = standard deviation. The assays in Table 12 used 2.5X more homogenized brain CJD than the assays in Table 13. The human plasma of control was the same for each set of experiments and showed previously not to contain the interfering material. The results demonstrate that the covalently bound peptoid reagent does not show any binding interference when different plasmas are used compared to the control plasma (and indeed shows higher signals than control plasma) compared to the biotinylated peptoid attached to the spheres SA that shows lower signals in a number of different plasmas. The pull-down / ELISA tests similar to those described above for the human sample were carried out on a variety of samples from different animal species including mouse, Syrian hamster and bighorn sheep (both the brain homogenate and blood samples from scrapie sheep and normal sheep were tested). For each of these species, the pathogenic form of the prion protein of that species was detected in samples from sick animals but not from non-diseased animals using the peptoid reagent of the invention.

Example 4 Sandwich ELISA A sandwich ELISA was developed to measure PrPc present in human plasma samples. To determine the levels of PrPSc present in human plasma, a sandwich ELISA was carried out using known amounts of recombinant human PrP protein (rPrP) to develop a standard curve (Figure IB). The amount of PrPC in increasingly high amounts of human plasma was determined using the standard curve with rPrP (FIG. IA). For the sandwich ELISA, 96-well microtiter plates were coated with the SAF32 mAb antibody (called "capture" antibody). This antibody binds to the octa-repeat region of human PrP, residues 23-90, and will bind to full lengths of PrPc and denatured PrPSc residues 23-2 = 31. The plate was blocked with casein for 1 hour at 37 ° C. To determine the PrPc levels in human plasma, different amounts of plasma were added to the plates coated with SFA32 and incubated for 2 hours at 37 ° C without agitation. The plates were washed and antibody 3F4 (antibody binding to human PrP residues 109-112) conjugated to the enzyme alkaline phosphatase ("detection" antibody, 3F4-AP) was added for 1 hour at 37 ° C. The plates were washed and chemiluminescence substrate was added and light units were counted after 30 minutes of incubation at 37 ° C. To quantify the amount of PrPc, the SAF32 coated plates were incubated with increasingly high concentrations of recombinant human PrP using the same sandwich ELISA format. Using the standard rPrP curve, the concentration of PrPc in this batch of human plasma was measured as being about 488 pg / 70 μl. Using this same sandwich ELISA, the specificity of the present peptoid reagents was evaluated to pull PrPSc or PrPc from a human plasma sample. The peptoid reagent Xllb was covalently conjugated to magnetic spheres (Dynabeads M-270 Carboxylic Acid) as described. Spheres coupled to the peptoid reagent were mixed for 1 hour in 100 ul of assay containing 70 ul human plasma, 1% Tween-20, 1% Triton X-100 and TBS. To investigate the specific downward traction of PrPSc, the experiment was repeated with plasma splashed with 0.05 μl of 10% brain homogenate (BH) prepared from a patient diagnosed with vCJD and as a control of a normal individual. After washing, the beads were treated with 15 μl of 3 M GdnSCN to flow and denature PrPSc. To prevent denaturation of capture antibody, GdnSCN was diluted with 210 μl of H20 and solution was added to the microtiter plate coated with SAF32, bringing the total volume of antigen to 250 μl. The experiment was carried out with 0.05 μl either 10% normal brain homogenate or 10% brain homogenate vCJD. The plates were washed and PrP was detected with 3F4-AP using a chemiluminescent AP substrate (LumiphosPlus). It was found that although the amount of PrPc in plasma, when directly detected (i.e., without any downward traction), measures around 887 LU, the amount of PrPc pulled with the peptoid reagent spheres contributes only to background levels of 23. LU The same applies when 0.05 μl of normal BH is splashed in 70 μl of plasma. When 0.05 μl of vCJD BH were splashed in 70 μl of plasma, a four-fold increase in signal could be detected. Using rPrP as standard curve it was found that the peptoid reagent spheres pulled 47 pg of PrP? C when they were splashed in plasma containing about 488 pg of PrPc, while the peptoid bound only 7 pg of PrPc, suggesting minimal 70-fold enrichment (table 14).

Table 14 Specific downward traction of PrP with peptoid reagent spheres Example 5 Denaturation of pH with sandwich ELISA As an alternative to dissociation using chaotropic agents for the dissociation and denaturing of the pathogenic prion after the descending traction stage, a process was developed that uses either a high pH or a high pH to carry out the dissociation / denaturation. The advantage of this method is that, unlike the situation with denaturing of GdnSCN, the conditions of denaturation of pH can be easily reversed without significantly increasing the volume in the reaction or introducing additional washing steps. The descending tractions were carried out as in Example 4 with magnetic spheres coupled in peptoid reagent Xllb with samples of 0.10 μl of vCJD 10% brain homogenate splashed in 100 μl of solution containing 70% human plasma. After mixing for 1 hour at 37 ° C, the beads were washed and treated under various pH conditions as indicated in table 15. As a control, 3M GdnSCN or Saline Tris pH Regulation (TBS) was used at pH 7.5 to treat the spheres. After 10 minutes of incubation at room temperature, the solutions were brought to neutral pH of about 7 as indicated in the table. Supernatant was added to a 96 well microtiter plate coated with SAF32 (capture antibody) and incubated for 12 hours at 47 ° C. 3F4 alkaline phosphatase-labeled antibody was used for detection as described in example 4. The descending traction samples that were treated with 3M GdnSCN for dissociation and denaturation of the spheres showed a signal from the plasma splashed with vCJD but not the control plasma, as exed. The treatment of the descending traction samples with pH regulator at pH 7.5 showed no significant signal or plasma splashed with vCJD or control plasma, as exed. The descending tensile samples were treated with solutions of various pH as shown. Several of the high pH and low pH treatments were able to dissociate and denature the prion protein of the spheres and treatment at pH 13 was efficient as the 3M GdnSCN. Significantly, although the volume of GdnSCN sample (after dilution) was 225 μl, the volume of the sample treated at pH 13 was only 75 μl after neutralization.

Table 15 Example 6 Denaturation of pH with direct ELISA Dissociation and denaturation at high and low pH were also tested in combination with a direct ELISA format using AP-labeled 3F4 antibody for detection. The process was carried out as in example 5 up to and including the neutralization step. The PrP in the supernatants was coated directly on the wells of the microtitre plates in a pH regulator of NaHCO 3 at pH 8.9 The plates were sealed and incubated overnight at 4 ° C. The next day the plate was washed, blocked with casein and PrP on the plate was detected with AP-labeled 3F4 using a chemiluminescent substrate. The results are shown in table 16.

Table 16 Example 7 Sandwich ELISA in magnetic spheres Typically, sandwich ELISA is carried out using 96-well polystyrene microtiter plates, where the capture antibody is coated on the plate and subsequently antigen binding, washing and detection is carried out. carried out in the same well. However, another format that uses magnetic spheres such as the solid phase matrix can be used. In this format, the magnetic spheres, which are coated with the capture antibody, are first mixed with the antigen, and then the detection antibody is added. To test whether the dissociation and pH denaturation procedure that had been developed for use with the ELISA plate could be used equally well with the magnetic spheres as the solid support, the following experiments were carried out. The down-traction of PrPSc from human plasma samples spiked using magnetic spheres coupled to peptoid reagent Xllb was carried out as previously described. The descending traction spheres were denatured with 50 μl of 0.1 N NaOH and neutralized with NaH2P04 (20 μl). The supernatant was transferred to a clean polypropylene well. To this solution were added new magnetic spheres that had been coated with anti-prion antibodies such as "capture" antibodies. A set of spheres was coated with 3F4 antibody, another set of spheres was coated with an antibody (C17) that recognizes an epitope on the C-terminal of the prion protein between residues 121 and 231. The spheres coated with antibody and the resulting eluent of the descending traction were incubated for 2 hours. The spheres were washed once and an AP-labeled detection antibody was detected. The antibody used for the detection antibody (C2) is one that binds to the octa-repeat region of PrP, residues 23-90. The spheres and the detection antibody were incubated for another 2 hours. The spheres were then washed and chemiluminescent AP substrate was added, mixed for 30 minutes and the chemiluminescence was measured with Luminoskan AFCENT (Thermo Labsytems). The ELISA using the same capture and detection antibodies in plaque format was carried out for a comparison. The results are shown in Table 17. In both formats and the presence of PrP? C in 1 or 10% of BH vCJD was detected after splashing and pulling the solution of 70 μL of plasma.

Table 17 Example 8 Peptides useful for designing peptoid reagents Non-limiting examples of peptides useful for making the peptoid reagents of the invention are derived from sequences shown in Table 18. The peptides in the table are represented by conventional one-letter amino acid codes and are illustrated with its amino terminus on the left and carboxy terminus on the right. Any of the sequences in the table can optionally include Gly linkers (Gn where n = 1, 2, 3 or 4) at the amino and / or carboxy terminus. The amino acids in square brackets indicate alternative residues that can be used in that position in different peptides. The round brackets indicate that the residues may be present or absent from the peptide reagent. The double round brackets (for example SEQ ID NO: 111) followed by a "2" indicate that the sequence includes two copies of the peptide between the double brackets. The residue following the copy designation number (eg, "K" in SEQ ID NO: 111) indicates the residue from which each copy of the peptide between the double parentheses extends. Thus, SEQ ID NO: 111 is a dimer of QWNKPSKPKTN peptide sequences (ie, SEQ ID NO: 14), each linked by its carboxy terminus to a lysine residue (K) by means of the functional groups a- and e -amino of lysine. The sequences that include "MAPS" indicate peptides with several antigenic sites. The number that precedes the term "branches" indicates the number of copies. Thus, SEQ ID NO: 112 contains 4 copies of GGGKKRPKPGGWNTGGG, which is SEQ ID NO: 67 with Gly linkers in each term, while SEQ ID NO: 113 contains 8 copies of GGGKKRPKPGGWNTGGG, which is again SEQ ID NO: 67 with Gly linkers in each term.

Table 18 Exemplary peptide sequences for making peptoid reagents of the invention EXAMPLE 9 Solid phase submonomer synthesis protocol for peptoids General Experiment. The solvents are reactive grade and are used without further purification. Bromoacetic acid was obtained from Aldrich (grade 99%) and DIC was obtained from Cheminplex International. All reactions and washes are carried out at 35 ° C unless otherwise indicated. Resin washing refers to the addition of a wash solvent (usually DMF or DMSO) to the resin, stirring the resin in such a way that a uniform suspension is obtained (typically for about 20 seconds), followed by a drain careful of the solvent of the resin. The solvents are best removed by vacuum filtration through the fritted bottom of the reaction vessel until the resin appears to be dry (typically about 10 seconds). Resin suspensions were agitated by bubbling argon through the bottom of the fritted container. The solvents used to dissolve reagents must be degassed before being used by sonication under housing vacuum for 5 minutes. For washing solvents, it is very convenient to have dispensers containing DMF, DMSO and dichloromethane available with adjustable volumes (1-5 mL). It is preferred not to stop a synthesis in the dimeric stage since the dimers can be cyclized after storage for a long period of time to form diketopiperazines. The preferred place to pause a synthesis is after the displacement washes.

Swelling of Initial Resin and Deprotection with Fmoc. A fritted reaction vessel is charged with 100 mg of Fmoc-Rink amide resin (0.50 mmol / g resin). To the resin, 2 mL of DMF is added and this solution is stirred for 5 minutes to swell the resin. A glass rod can be used to break pieces of resin, if necessary. The DMF is added later. The Fmoc group is then removed by adding 2 mL of 20% piperidine in DMF to the resin. This is stirred for 1 minute, then drained. Another 2 mL of 20% piperidine in DMF is added to the resin and stirred for 20 minutes, and then drained. The resin is then washed with DMF (5 x 2 mL).

Submonomer Synthesis Cycle. The amine unblocked by adding 1.13 mL of 1.2 M bromoacetic acid in DMF to the resin, followed by 200 μL (0.93 equivalents) of concentrated n, N '-diisopropylcarbodiimide (DIC). This solution is stirred for 20 minutes at 35 ° C, then drained. The resin is then washed with DMF (3 x 2 mL).

STAGE 1 STAGE 2 The acylation step is then followed by nucleophilic displacement with a primary amine. To the washed resin is added 0.85 mL of a 1 M solution of the amine in NMP. This solution is stirred for 30 minutes at 35 ° C and then drained. The resin is then washed with DMF (2 x 2 mL). This completes a reaction cycle. The acylation / displacement cycle is repeated until the desired oligomer is obtained, for example, about 3 to about 30 times.

Conjugation of Biotin and Tiol Groups.

Optionally, biotin was coupled to the N terminus by the addition of 2.0 mL of a solution of biotin (0.4 M) and HOBt (0.4 M) in DMSO, followed by the addition of 1.05 equivalents of concentrated DIC. The reaction mixture was stirred for 1 hour at 35 ° C, after which the reaction mixture was drained and the resin was washed with DMSO (2 x 3 mL) followed by DMF (3 x 2 mL). Optionally, a thiol group was incorporated by the incorporation of cysteine, which was added by means of an amino acid coupling step: Fmoc-Cys (Trt) (NovaBiochem) was coupled to the N terminus by the addition of 2.0 mL of a solution of Fmoc-Cys (Trt) (0.4 M) and HOBt (0.4 M) in DMF, followed by the addition of 1.05 equivalents of concentrated DIC. The reaction mixture was stirred at 35 ° C for 1 hour, after which the reaction mixture was drained and the resin was washed with DMF (3 x 3 mL). The Fmoc group is then removed by adding 2 mL of 20% piperidine in DMF to the resin. This is stirred for 1 minute, then drained. Another 2 mL of 20% piperidine in DMF is added to the resin and stirred for 20 minutes, then drained. The resin is then washed with DMF (5 x 2 mL).

Cutting (for 50 μmoles of resin). After the synthesis reaction and the resin wash, the resin is washed with dichloromethane (2 x 2 mL) and air dried for 1 minute. The dried resin is placed in a glass scintillation flask containing a Teflon micro-agitation rod, and about 5 mL of TFA / triisopropylsilane / water 95 / 2.5 / 2.5 (v / v / v) are added. This solution is stirred for 15 minutes. The cut sample is filtered for each sample through an 8 mL solid phase extraction (SPE) column equipped with 20 μm polyethylene frit inside a 50 mL polypropylene conical centrifuge tube. The resin is then washed with 1 mL of 95% TFA and the filtrates are combined. The filtrate is then diluted with an equal volume of water in the centrifuge tube. This solution is then frozen and lyophilized to dryness. The dried product is then collected in 10 mL of 1: 1 acetonitrile / water acid and again lyophilized to dryness.

Characterization of Oligomers. The individual peptoid oligomers are analyzed by reverse phase HPLC on a C-18 column (Vydac, 5 μm, 300 Á, 4.5 × 250 mm). A linear gradient of 0-80% B in 40 minutes is used at a flow rate of 1 mL / min. (solvent A = 0.1% TFA in water, solvent B = 0.1% TFA in acetonitrile). The major peaks are collected and subjected to the electrospray MS analysis to determine the molecular weights.

Purification of Peptoides. The peptoids are purified by reverse phase HPLC before being used by biologists. Typically these compounds are analyzed and purified on a C18 column. Thus, the compounds are dissolved in a small amount of 10% acetonitrile / water and purified on a 50 x 20 mm ID DuraGel HS C18 column (Peeke Scientific). A linear gradient of 5-65% B is used in 40 minutes at a flow rate of 30 mL / min. (solvent A = 0. 1% TFA in water, solvent B = 0.1% TFA in acetonitrile). The combined product fractions are combined and lyophilized to a white powder.

EXAMPLE 10 Efficacy of downward traction of peptoid reagent Xllb The capacity of the reagent. Xllb peptoide covalently bonded to spheres was tested by the descending tensile test as described below. Homogenate brain with vCJD or normal (BH) was splashed in 50% normal human plasma pooled in TBS with 1% Tween 20 and 1% triton-X 100. The uncontrolled samples were not splashed with either. Then 100 μl of each sample (containing 10 nL or none of 10% BH) were mixed with 3 μ of Xllb spheres (30 mg / mL) and the resulting mixture was incubated at 37 ° C for 1 hour with constant agitation to . 750 rpm. The spheres were then washed four times with TBST containing 0.05% Tween 20 and PrPSc bound to the spheres was dissociated by the addition of 0.1 N NaOH. The denatured prion protein was neutralized later by 0.3 M NaH2P04 and transferred to an ELISA plate. The downward traction efficiency was calculated by comparing the signals from the downward traction samples with those from identical samples that were denatured by guanidinium thiocyanate (GdnSCN without any downward traction) The vCJD or normal brain prion protein was denatured by mixing volume equal to 5% of BH and 6 M GdnSCN, and incubated at room temperature for 10 minutes The sample was then diluted in TBST to the same concentration of the descending traction samples, with TBST only as control 100 μL of each sample directly denatured were then transferred to the same ELISA plate for the descending traction samples.The ELISA plate was coated by capture antibody 3F4 at 2.5 μg / mL in 0.1M NaHCO 3 The coating procedure was carried out at 4 °. C overnight, and then washed three times by TBST.The plate was then blocked by 1% casein in TBS at 37 ° C for 1 hour. Prionic rotein from both directly denatured and tensile samples were incubated to an ELISA plate with 3F4 for 1 hour at 37 ° C, with constant agitation at 300 rpm, and the plate was washed six times with TBST. Detection antibody conjugated to alkaline phosphatase (AP) was diluted to 0.1 μg / mL in 0.1% casein in TBST, and then added to an ELISA plate. The plate was incubated later at 37 ° C for 1 hour, and washed six times by TBST. The signal was developed using improved chemiluminescent substrate, and read by a luminometer in relative light units (RLU). The results are shown in Table 19. Prion protein of brain tissue can be completely denatured by 3 M GdnSCN and detected by its antibody. In this experiment, the signal generated by the downward traction of prion protein using Xllb spheres was compared with the signal obtained from protein directly denatured by GdnSCN. The data showed that the background (without BH) for the directly denatured and downward traction samples was 9.0 and 7.7 RLU respectively. 10 nL of directly denatured 10% normal BH had a signal of 14.6 RLU, reflecting the level of PrPc in normal brain. Meanwhile, 10 nL of 10% of normal BH detected by the descending traction method showed the reading of 9.9 RLU, which is similar to its background. This demonstrated the specificity of the peptoide Xllb. When 10 nL of 10% of vCJD sample were tested by direct tensile and direct denaturing methods, the data showed 53.0 and 56.3 of RLU, which means that the downward traction efficiency of Xllb spheres reached almost 100%.

Table 19 Example 11 Distinction of prion strains Structural differences between prion strains can be detected by measuring their different properties of thermodynamic unfolding. Incubation of PrPSc with increasingly high concentrations of chemical denaturing can produce a denaturation profile of the prion shaper that is characteristic of each strain. Previous studies used proteinase K (PK) resistance to measure the proportion of PrPSc that remained bent after treatment with denaturant. Here, it was tested whether the peptoid reagent Xllb could also be used to distinguish bent and unfolded PrPSc, thus allowing the measurement of conformation states in PK-sensitive strains when the denaturing profiles could not be measured by conventional methods. To generate a denaturing profile for a strain of vCJD, a brain homogenate vCJD (NIBSC CJD Resource Center) was incubated with various concentrations of guanidine hydrochloride before the samples were diluted and subjected to downward traction using peptoid reagent Xllb (see Example 3 and description of traction Xllb below). The material bound to Xllb was then eluted and detected by sandwich ELISA assay. A graphical representation of PrPSc pulled at each concentration of denaturant showed that the concentration of guanidine hydrochloride was inversely proportional to the fraction of folded PrPSc pulled by Xllb. The data points formed a single sigmoid curve suggesting the existence of a PrPSc conformer in the brain homogenate that unfolds in a larger transition (see figure 4, open points). Therefore, it is believed that Xllb recognizes a structural epitope in PrPSc that is broken after treatment with chemical denaturing. Analysis of a sporadic CJD strain (sCJD, NIBSC CJD Resource Center) yielded a similar sigmoid curve that was shifted to the right of the denaturing profile for vCJD (see Figure 4, gray dots), illustrating that the recognized structural epitope by Xllb is believed to be more stable in the sCJD strain when compared to the vCJD strain. The analysis of each strain consistently produced the equivalent pattern, allowing the definition of the curve with a characteristic value as a measure of the relative conformation stability of PrPSc: The concentration of GdnHCl found at maximum mean denaturation (GdnHCl? / 2). The denaturation profile of vCJD had a GdnHCl? / 2 of 1.6 M GdnHCl. In contrast, a brain homogenate from sCJD was more stable to denaturing with guanidine, with a GdnHCl? 2 of 2.0 M GdnHCl. Therefore, Xllb can be used as a tool to dissect a conformational variability between prion strains.

Downward traction with Xllb Homogenate of infectious brain (75-200 nL, 10%) was denatured in guanidine solutions that varied in concentrations of 0-4 M for 1 hour at room temperature. After denaturation, all samples were adjusted to a final concentration of 0.1 M guanidine hydrochloride in TBSTT, and bent PrPSc was pulled with Xllb spheres using standard descending methods. The drawn material was eluted and measured by sandwich ELISA assay in triplicate with C17 capture antibodies and 3F4-AP detection antibodies. As those skilled in the art will appreciate, numerous changes and modifications can be made to the preferred embodiments of the invention without departing from the spirit thereof. It is intended that all these variations be within the scope of the invention. It is also intended that each of the patents, applications and printed publications, including books, mentioned in this patent document are hereby incorporated by reference in their entirety.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (52)

1. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A peptoid reagent that preferentially interacts with a pathogenic form of a conformation disease protein as compared to a non-pathogenic form of the conformation disease characterized in that it has the formula: Xa- (Q) n-Xb wherein: each Q is independently an amino acid or an N-substituted glycine, and - (Q) n- defines peptoid region; Xa is H, (C? -C6) alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, acyl (C? -C6), aminoacyl (Ci?), An amino acid, an amino protecting group or a polypeptide of 2 to about 100 amino acids, wherein Xa is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety; Xb is H, (C? -C6) alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (Ci-C?) Alkoxy, aryloxy, aralkoxy, a carboxy protective group, an amino acid or a polypeptide of 2 to about 100 amino acids, wherein Xb is optionally substituted by a conjugated moiety that optionally binds through a linker portion; and n is 3 to about 30; wherein at least about 50% of the peptoid region - (Q) n- comprises N-substituted glycines.
2. 2. The peptoid reagent according to claim 1, characterized in that the N-substituted glycine has the formula: - (NR-CH2-C0) - wherein each R is independently selected from (C2-C6) alkyl, haloalkyl (C? -C6), (C2-C6) alkenyl ,. alkynyl of (C2-Ce), cycloalkyl-aryl of (Cd-Cio), aminoalkyl of (C? -C6), onioalkyl of (C? -C6), hydroxyalkyl of (C? -C6), alkoxy of (Ci) -Cβ) -alkyl (Ci-C?), Carboxy, carboxyalkyl of (C2-C6), carbamylalkyl of (C2-C6), guanidino, guanidinoalkyl of (C? -C6), amidinoalkyl of (Ci-C?), thiol, (Ci-Cd) alkylthiol, alkylthioalkyl of 2-10 carbon atoms, heterocyclyl containing N, heterocyclylalkyl of (C? -C6) containing N, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyl-alkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms and arylalkyl of (Ci-Cd); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C? -C6) alkoxy.
3. 3. The peptoid reagent according to claim 1, characterized in that Xb is an amino acid optionally substituted by a conjugated portion that is optionally linked through a linker portion.
4. 4. The peptoid reagent according to claim 1, characterized in that n is about 5 to about 15.
5. The peptoid reagent according to claim 1, characterized in that each Q is an N-substituted glycine.
6. 6. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- is polyionic at a physiologically relevant pH.
7. 7. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- has a net charge of at least 3+ at a physiologically relevant pH.
8. 8. The peptoid reagent according to claim 1, characterized in that the N-substituted glycine has the formula: - (NR-CH2-C0) -, wherein R is independently selected from (C2-C6) alkyl, haloalkyl (Ci-Cß), alkenyl of (C2-C6), alkynyl of (C2-C6), cycloalkyl-aryl of (C6-C? 0), aminoalkyl of (Ci-Ce), ammonioalkyl of (Ci-Cg), hydroxyalkyl of (C? -C6), (C? -C6) alkoxy-(C? -C6) alkyl, carboxy, carboxyalkyl of (C2-C6), carbamyl, carbamylalkyl of (C2-C6), guanidino, guanidinoalkyl of (C? -C6), amidino, (Ci-C6) amidinoalkyl, thiol, (C? -C6) alkylthiol, alkylthioalkyl of 2-10 carbon atoms, N-containing heterocyclyl, (Ci-C?) heterocyclylalkyl containing N, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms, indolyl, indolyalkyl of 9-15 carbon atoms, naphthyl, naphthylalkyl of 11-16 carbon atoms and arylalkyl of (C? -C6); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C? -C6) alkoxy, and the peptoid region - (Q) n ~ comprises at least 3 or N-substituted glycines wherein R is a portion that is charged at a physiologically relevant pH.
9. 9. The peptoid reagent according to claim 1, characterized in that the charged N-substituted glycines comprise a charged portion R which is independently selected from aminoalkyl of C? -C6), ammonioalkyl of (C? -C6), guanidino, guanidinoalkyl of (Ci-C6), amidino, amidinoalkyl of (C? -C6), heterocyclyl containing N and heterocyclylalkyl of (C? -C6) containing N, wherein each R portion is optionally substituted with 1-3 independently selected substituents of halogen, C? -C3 methoxy and C? -C3 alkyl.
10. 10. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- comprises SEQ ID NO: 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240 or 241.
11. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- comprises SEQ ID NO: 229, 230, 232, 233, 237, 238, 239 or 240.
12. 12. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- comprises SEQ ID NO: 230, 237, 238, 239 or 240.
13. 13. The peptoid reagent according to claim 1, characterized in that the peptoid region - (Q) n- comprises SEQ ID NO: 240.
14. The peptoid reagent according to claim 1, characterized in that it comprises at least one conjugated portion.
15. 15. The peptoid reagent according to claim 14, characterized in that the conjugated portion is linked through a linker portion.
16. 16. The peptoid reagent according to claim 14, characterized in that the conjugated portion is an entanglement agent or a binding agent.
17. 17. The peptoid reagent according to claim 14, characterized in that the conjugated portion comprises biotin or a mercapto group.
18. 18. The peptoid reagent according to claim 1, characterized in that the conformation disease protein is that of a prion-related disease, the pathogenic form of the conformation disease protein is PrPSc and the non-pathogenic form of the protein of conformation disease is PrPc.
19. 19. The peptoid reagent according to claim 1, characterized in that the pathogenic form of the conformation disease protein interacts with an affinity at least about 10 times greater than that for the non-pathogenic form of the conformation disease protein.
20. 20. A peptoid reagent that preferably interacts with PrPSc compared to PrPc, characterized in that it has the formula: Xa- (Q) n-Xb wherein: each Q is independently an N-substituted glycine having the formula: - (NR -CH2-CO) -where each R is independently selected from (C2-C6) alkyl, (C? -C6) haloalkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, cycloalkyl-aryl of (Cd-Cio), aminoalkyl of (C? -C6), ammonioalkyl of (C? -C6), hydroxyalkyl of (C? -C6), alkoxy of (C? -C6) -alkyl of (Ci-C6) , carboxy, carboxyalkyl of (C2-C6), carbamyl, carbamylalkyl of (C2-C6), guanidino, guanidinoalkyl of (C? -C6), amidino, amidinoalkyl of (C? -C6), thiol, alkylthiol of Cd), alkylthioalkyl of 2-10 carbon atoms, heterocyclyl containing N, heterocyclylalkyl of (C? -C6) containing N, imidazolyl, imidazolylalkyl of 4-10 carbon atoms, piperidyl, piperidylalkyl of 5-10 carbon atoms , indolyl, indolyl-alkyl of 9-15 a atoms of carbon, naphthyl, naphthylalkyl of 11-16 carbon atoms and arylalkyl of (Ci-Cß); wherein each R portion is optionally substituted with 1-3 substituents independently selected from halogen, hydroxy and (C? -C6) alkoxy; and - (Q) n- defines a peptoid region; Xa is H, (Ci-Ce) alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, acyl (C? -C6), aminoacyl of (C? _6), an amino acid, an amino protecting group or an polypeptide of 2 to about 100 amino acids, wherein Xa is optionally substituted by a conjugated moiety that is optionally linked through a linker moiety; X is H, (C? -C6) alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, amino, alkylamino, dialkylamino, hydroxyl, (C? -C6) alkoxy, aryloxy, aralkoxy, a carboxy protective group, a amino acid or a polypeptide of 2 to about 100 amino acids, wherein Xb is optionally substituted by a conjugated moiety that optionally binds through a linker portion; and n is 4, 5, 6, 7 or 8; wherein the peptoid region - (Q) n- has a net charge of at least 3+ at physiologically relevant pH.
21. 21. A peptoid reagent characterized in that it is selected from: p IV vp IX Xla Xlb Xlla Xllb XIII
22. 22. A peptoid reagent characterized because it is selected from: IX X Xla Xlb Xlla Xllb or salts thereof.
23. 23. A complex characterized in that it comprises the peptoid reagent according to any of claims 1, 10, 20 or 21 and a pathogenic prion.
24. 24. A composition characterized in that it comprises the peptoid reagent according to any of claims 1, 10, 20 or 21 attached to a solid support.
25. 25. A composition characterized in that it comprises the peptoid reagent according to any one of claims 1, 10, 20 or 21 and a sample.
26. 26. The composition according to claim 25, characterized in that the sample is a biological sample.
27. 27. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the Peptide proto-peptide reagent, if present, to form a complex, and detect complex formation, where the formation of the complex is indicative of the presence of the pathogenic prion.
28. 28. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptoid reagent, if present, to form a first complex, contacting the first complex with the second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the attachment of the second peptoid reagent to the prion pathogen of the first complex to form a second complex, and detect the formation of a second complex, wherein the formation of the second complex is indicative of the presence of the pathogenic prion.
29. 29. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptide reactive reagent, if present, to form a first complex, remove unbound sample from the first complex, contact the first complex with a second peptoid reagent of the invention, optionally labeled in detectable form, under conditions that allow the binding of the second peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, wherein the formation of the second complex is indicative of the presence of the pathogenic prion.
30. 30. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the First protogenic peptoid reactive reagent, if present, to form a first complex, remove the unbound sample from the first complex, dissociate the pathogenic prion from the first complex in this manner by providing a dissociated pathogenic prion, contacting the dissociated pathogenic prion with a second peptoid reagent according to claim 1, optionally labeled in detectable form, under conditions that allow the attachment of the second peptoid reagent to the dissociated pathogenic prion to form a second complex, and detect the formation of the second complex, where the formation of the second complex is indicative of the presence of the pathogenic prion.
31. 31. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptoid reactive reagent, if present, to form a first complex, contacting the first complex with a prion binding reagent, optionally labeled in detectable form, under conditions that allow binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex and detect the formation of the second complex, where the formation of the second complex is indicative of the presence of the pathogenic prion.
32. 32. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptoid reagent, if present, to form a first complex, remove the unbound sample from the first complex, contact the first complex with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the pathogenic prion of the first complex to form a second complex, and detecting the formation of the second complex, wherein the formation of the second complex is indicative of the presence of the pathogenic prion.
33. 33. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptoid reactive reagent, if present, to form a first complex, remove unbound sample from the first complex, dissociate the pathogenic prion from the first complex thereby providing a dissociated pathogenic prion, contact the dissociated pathogenic prion with a prion binding reagent, optionally labeled in detectable form, under conditions that allow the binding of the prion binding reagent to the dissociated pathogenic prion to form a second complex, and detect the formation of the second complex, wherein the formation of the second complex is Indicator of the presence of the pathogenic prion.
34. 34. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding of the first protogenic peptoid reactive reagent, if present, to form a first complex, remove the unbound sample, dissociate the pathogenic prion from the first complex thus providing a first dissociated pathogen, contact the dissociated pathogenic prion with a binding reagent prions under conditions that allow the binding of the prion binding reagent to the dissociated pathogenic prion to form a second complex, and detect the formation of the second complex using a second prion binding reagent, optionally labeled in detectable form, wherein the formation of the second complex is indicative of the presence of the pathogenic prion.
35. 35. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises contacting the master with a prion binding reagent under conditions that allow the binding of the prion binding reagent to the pathogenic prion, if present, to form a first complex, remove the unbound sample from the first complex, contact the complex with the first peptoid reagent according to any of claims 1 to 22, optionally labeled in detectable form, under conditions that allow the binding of the peptoid reagent to the pathogenic prion of the first complex to form a second complex, and detect the formation of the second complex, wherein the formation of the second complex is indicative of the presence of the pathogenic prion.
36. 36. The method according to any of claims 31 to 35, characterized in that the prion binding reagent comprises an anti-prion antibody.
37. 37. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises: contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding from the first peptoid reagent to the pathogenic prion, if present, to form a complex, remove the non-bound sample from the complex, dissociate the pathogenic prion from the complex thus providing a dissociated pathogenic prion, contact the dissociated pathogenic prion with a second solid support under conditions that allow the dissociated pathogen prion to adhere to the second solid support and detect the dissociated and adhered pathogenic prion using a prion binding reagent, optionally labeled in detectable form, wherein the binding of the prion binding reagent indicates the presence of the prion pathogen
38. 38. The method according to claim 37, characterized in that the dissociation is carried out by exposing the complex to high pH or low pH.
39. 39. The method according to claim 38, characterized in that it further comprises the step of neutralizing the high pH or the low pH after dissociation.
40. 40. The method according to claim 37, characterized in that the dissociated pathogenic prion is denatured.
41. 41. The method according to claim 37, characterized in that the prion binding reagent comprises an anti-prion antibody.
42. 42. A method for detecting the presence of a pathogenic prion in a sample, characterized in that it comprises: contacting the sample with a first peptoid reagent according to any of claims 1, 10, 20 or 21 under conditions that allow the binding from the first peptoid reagent to the pathogenic prion, if present, to form a first complex, remove the unbound sample from the first complex, dissociate the pathogenic prion from the first complex thereby providing a dissociated pathogenic prion, contact the dissociated pathogenic prion with a second solid support, wherein the second solid support comprises a first anti-prion antibody, under conditions that allow the dissociated pathogen prion to bind to the first anti-prion antibody to form a second complex and detect the pathogenic prion dissociated from the second complex with a second anti-prion antibody, optionally labeled in detectable form, wherein the binding of the second Anti-prion antibody indicates the presence of the pathogenic prion.
43. 43. The method according to claim 42, characterized in that the dissociation is carried out by exposing the first complex at high pH or low pH.
44. 44. The method according to claim 43, characterized in that it further comprises the step of neutralizing the high pH or the low pH after dissociation.
45. 45. The method according to claim 42, characterized in that the dissociated pathogenic prion is denatured.
46. 46. The method according to claim 42, characterized in that the first prion binding reagent comprises an anti-prion antibody.
47. 47. The method according to claim 42, characterized in that the second prion binding reagent comprises an anti-prion antibody.
48. 48. A method for determining a location of an infection by prion-related disease in an animal, characterized in that it comprises: (a) administering to the animal the peptoid reagent according to any of claims 1 to 22, wherein the peptoid reagent is linked to an imaging agent and (b) detecting the imaging agent, wherein the detection of the imaging agent determines the location of the infection.
49. 49. A method for isolating a pathogenic prion from a sample, characterized in that it comprises: (a) contacting a solid support comprising the peptoid reagent according to any of claims 1, 10, 20 or 21 with the sample under that allow the binding of the pathogenic prion, if present in the sample, to the peptoid reagent to form a complex, and (b) remove the non-bound sample from the complex, thereby providing an isolated pathogenic prion.
50. 50. A method for reducing the amount of pathogenic prions in a sample, characterized in that it comprises: (a) contacting a solid support comprising the peptoid reagent according to any of claims 1, 10, 20 or 21 with the sample under conditions that allow binding of the pathogenic prion, if present in the sample, to the peptoid reagent of the solid support to form a complex, and (b) separating non-bound sample from the complex, thereby providing the sample with a reduced amount of pathogenic prion.
51. 51. A method for preparing a source of blood that is substantially free of a pathogenic prion, characterized in that it comprises: (a) detecting the presence or absence of a pathogenic prion in a plurality of blood samples, wherein detection includes binding of the pathogenic prion, if present, to the peptoid reagent according to any of claims 1, 10, 20 or 21 and (b) combining the samples in which the pathogenic prion is not detected, thereby providing the blood source which is substantially free of the pathogenic prion.
52. 52. A method for preparing a food source that is substantially free of a pathogenic prion, characterized in that it comprises: (a) detecting the presence or absence of a pathogenic prion in a plurality of food samples, wherein the detection includes the binding of the pathogenic prion, if present, to the peptoid reagent according to any of claims 1, 10, 20 or 21 and (b) combining the samples in which the pathogenic prion is not detected, thereby providing the food source which is substantially free of the pathogenic prion.