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WO2001096568A1 - Nouveau polypeptide, proteine humaine de liaison 51 d'une proteine precurseur de l'amyloide, et polynucleotide codant ce polypeptide - Google Patents

Nouveau polypeptide, proteine humaine de liaison 51 d'une proteine precurseur de l'amyloide, et polynucleotide codant ce polypeptide Download PDF

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Publication number
WO2001096568A1
WO2001096568A1 PCT/CN2001/000780 CN0100780W WO0196568A1 WO 2001096568 A1 WO2001096568 A1 WO 2001096568A1 CN 0100780 W CN0100780 W CN 0100780W WO 0196568 A1 WO0196568 A1 WO 0196568A1
Authority
WO
WIPO (PCT)
Prior art keywords
polypeptide
polynucleotide
precursor protein
binding protein
amyloid precursor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2001/000780
Other languages
English (en)
Chinese (zh)
Inventor
Yumin Mao
Yi Xie
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Biowindow Gene Development Inc
Original Assignee
Shanghai Biowindow Gene Development Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Biowindow Gene Development Inc filed Critical Shanghai Biowindow Gene Development Inc
Priority to AU87509/01A priority Critical patent/AU8750901A/en
Publication of WO2001096568A1 publication Critical patent/WO2001096568A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein

Definitions

  • Alzheimer's disease is characterized by a reduction in the number of neurons and an increase in P amyloid bodies in the brain.
  • P amyloid bodies are composed of beta-amylo id peptide (AP).
  • AP is about 4kDa in size and is a soluble protein hydrolysate processed from ⁇ -amylloid protein in precur sor (APP).
  • APP precur sor
  • Another object of the invention is to provide a polynucleotide encoding the polypeptide.
  • the present invention relates to an isolated polypeptide, which is of human origin and comprises: a polypeptide having the amino acid sequence of SEQ ID No. 2, or a conservative variant, biologically active fragment or derivative thereof.
  • the polypeptide is a polypeptide having the amino acid sequence of SEQ ID NO: 2.
  • the invention also relates to an isolated polynucleotide comprising a nucleotide sequence or Its variant:
  • “Deletion” refers to the deletion of one or more amino acids or nucleotides in an amino acid sequence or nucleotide sequence.
  • Complementary refers to the natural binding of polynucleotides by base-pairing under conditions of acceptable salt concentration and temperature.
  • sequence C-T-G-A
  • complementary sequence G-A-C-T.
  • the complementarity between two single-stranded molecules may be partial or complete.
  • the degree of complementarity between nucleic acid strands has a significant effect on the efficiency and strength of hybridization between nucleic acid strands.
  • the present invention also relates to a vector comprising the polynucleotide of the present invention, and a host cell that is genetically engineered using the vector of the present invention or directly using a human starch precursor protein binding protein 51 coding sequence, and that the present invention is produced by recombinant technology Polypeptide method.
  • the expression vector preferably contains one or more selectable marker genes to provide phenotypic traits for selection of transformed host cells, such as dihydrofolate reductase, neomycin resistance, and green for eukaryotic cell culture.
  • selectable marker genes to provide phenotypic traits for selection of transformed host cells, such as dihydrofolate reductase, neomycin resistance, and green for eukaryotic cell culture.
  • GFP fluorescent protein
  • tetracycline or ampicillin resistance for E. coli.
  • Growth and development disorders mental retardation, brain development disorders, skin, fat and muscular dysplasia, bone and joint dysplasia, various metabolic deficiencies, stunting, dwarfism, Cushing syndrome, Sexual retardation
  • Abnormal expression of the human amyloid precursor protein-binding protein 51 of the present invention may also cause certain hereditary, hematological diseases, and the like.
  • human amyloid precursor protein binding protein 51 may be added to a bioanalytical assay to determine the interaction between human amyloid precursor protein binding protein 51 and its receptor by determining the compound Influence to determine if a compound is an antagonist.
  • Receptor deletions and analogs that act as antagonists can be screened in the same way as for screening compounds described above.
  • Polypeptide molecules capable of binding to human starch precursor protein-binding protein 51 can be obtained by screening a random peptide library composed of various possible combinations of amino acids bound to a solid phase. When screening, the human amyloid precursor protein binding protein 51 molecule should generally be labeled.
  • Antibodies can also be used to design immunotoxins that target a particular part of the body.
  • human amyloid precursor protein binding protein 51 high affinity monoclonal antibodies can interact with bacterial or plant toxins (such as diphtheria toxin, ricin Protein, ormosine, etc.) covalently bind.
  • a common method is to attack the amino group of an antibody with a thiol cross-linking agent such as SPDP and bind the toxin to the antibody through the disulfide exchange.
  • This hybrid antibody can be used to kill human starch precursor protein binding protein 51 positive cells.
  • Polynucleotides encoding human amyloid precursor protein binding protein 51 can also be used for a variety of therapeutic purposes. Gene therapy technology can be used to treat abnormal cell proliferation, development or metabolism caused by the non-expression or abnormal / inactive expression of human amyloid precursor protein binding protein 51.
  • Recombinant gene therapy vectors (such as viral vectors) can be designed to express mutated human amyloid precursor protein binding protein 51 to inhibit endogenous human amyloid precursor protein binding protein 51 activity.
  • a variant human amyloid precursor protein-binding protein 51 may be a shortened human amyloid precursor protein-binding protein 51 that lacks a signaling domain. Although it can bind to downstream substrates, it lacks signal transduction. active.
  • Primerl 5,-GGAAGCAGTGCAGAGAGGAGAGCG -3, (SEQ ID NO: 3)
  • the above specific tissues are thymus, testis, muscle, spleen, lung, skin, thyroid, liver, PMA + Ecv304 cell line, PMA-Ecv304 cell line, non-starved L02 cell line, L02 cell line stimulated by arsenic for 1 hour, L02 cell line stimulated by arsenic for 6 hours prostate, heart, lung cancer, fetal bladder, fetal small intestine, fetal large intestine, fetal thymus, fetal muscle, fetal liver, fetal kidney, fetal spleen, fetal brain, Fetal lung and fetal heart.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Neurology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biomedical Technology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un nouveau polypeptide, une protéine humaine de liaison 51 d'une protéine précurseur de l'amyloïde, et un polynucléotide codant ce polypeptide ainsi qu'un procédé d'obtention de ce polypeptide par des techniques recombinantes d'ADN. L'invention concerne en outre les applications de ce polypeptide dans le traitement de maladies, notamment des tumeurs malignes, de l'hémopathie, de l'infection par VIH, de maladies immunitaires et de diverses inflammations. L'invention concerne aussi l'antagoniste agissant contre le polypeptide et son action thérapeutique ainsi que les applications de ce polynucléotide codant la protéine humaine de liaison 51 d'une protéine précurseur de l'amyloïde.
PCT/CN2001/000780 2000-05-16 2001-05-14 Nouveau polypeptide, proteine humaine de liaison 51 d'une proteine precurseur de l'amyloide, et polynucleotide codant ce polypeptide Ceased WO2001096568A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU87509/01A AU8750901A (en) 2000-05-16 2001-05-14 A novel polypeptide, a human 51-binding amyloid precursor protein and the polynucleotide encoding the polypeptide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN 00115729 CN1323833A (zh) 2000-05-16 2000-05-16 一种新的多肽——人淀粉类前体蛋白结合蛋白51和编码这种多肽的多核苷酸
CN00115729.9 2000-05-16

Publications (1)

Publication Number Publication Date
WO2001096568A1 true WO2001096568A1 (fr) 2001-12-20

Family

ID=4585173

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2001/000780 Ceased WO2001096568A1 (fr) 2000-05-16 2001-05-14 Nouveau polypeptide, proteine humaine de liaison 51 d'une proteine precurseur de l'amyloide, et polynucleotide codant ce polypeptide

Country Status (3)

Country Link
CN (1) CN1323833A (fr)
AU (1) AU8750901A (fr)
WO (1) WO2001096568A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1206421A (zh) * 1995-11-01 1999-01-27 科斯药品公司 载脂蛋白e2和阿尔采默氏病的治疗
WO2000002911A2 (fr) * 1998-07-10 2000-01-20 Curagen Corporation INTERACTION DE PRECURSEUR DE LA PROTEINE BETA-AMYLOIDE HUMAINE (β-APP) ET DE PROTEINE HUMAINE DU TYPE LON-PROTEASE (HsLON)

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1206421A (zh) * 1995-11-01 1999-01-27 科斯药品公司 载脂蛋白e2和阿尔采默氏病的治疗
WO2000002911A2 (fr) * 1998-07-10 2000-01-20 Curagen Corporation INTERACTION DE PRECURSEUR DE LA PROTEINE BETA-AMYLOIDE HUMAINE (β-APP) ET DE PROTEINE HUMAINE DU TYPE LON-PROTEASE (HsLON)

Also Published As

Publication number Publication date
AU8750901A (en) 2001-12-24
CN1323833A (zh) 2001-11-28

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