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DK2332968T3 - Alpha-helix peptider egnede til aktivering eller inhibering af celledød - Google Patents

Alpha-helix peptider egnede til aktivering eller inhibering af celledød Download PDF

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Publication number
DK2332968T3
DK2332968T3 DK10195495.6T DK10195495T DK2332968T3 DK 2332968 T3 DK2332968 T3 DK 2332968T3 DK 10195495 T DK10195495 T DK 10195495T DK 2332968 T3 DK2332968 T3 DK 2332968T3
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Loren D Walenski
Gregory Verdine
Stanley J Korsmeyer
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Dana Farber Cancer Inst Inc
Harvard College
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
    • C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
    • C—CHEMISTRY; METALLURGY
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    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • 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
    • C07K14/4747—Apoptosis related proteins
    • C—CHEMISTRY; METALLURGY
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    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64—Cyclic peptides containing only normal peptide links

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Claims (16)

1. α-helix polypeptid egnet til aktivering eller inhibering af celledød af formel (I):
Formel I hvor: hver Ri og R2 er uafhængigt H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, arylalkyl, cykloalkylalkyl, heteroarylalkyl, eller heterocyklylalkyl; R3 er et tværbindingsmiddel som er C1-C20 alkyl, C2-C20 alkenyl, eller C2-C20 alkynyl; hvor R3 er substitueret med 0-6 Rs; R5 er halo, alkyl, OR6, N(Re)2, SRe, SOR6, SO2R6, CO2R6, Re, et epoxid, en fluorescerende del, eller en radioisotop; Re er H, alkyl, eller et terapeutisk middel; x er et heltal valgt fra 2, 3 eller 6; hver y er uafhængigt et heltal fra 0-100; z er et heltal fra 1-10; og hver Xaa er uafhængigt en alpha-aminosyre; og hvor polypeptidet er transporteret eller aktivt transporteret igennem en cellemembran, som bestemt i et assay omfattende at forberede fluorescensmærket polypeptid, at påføre det fluorescensmærkede polypeptid til en intakt celle, og at undersøge cellen for cellulær fluorescens ved mikroskopi eller high-throughput cellulær fluorescensdetektion.
2. Polypeptidet ifølge krav 1, hvor Ri og R2 er H eller Ci-6alkyl.
3. Polypeptidet ifølge krav 1, hvor R3 er ligekædet alkyl, alkenyl eller alkynyl.
4. Polypeptidet ifølge krav 1, hvor R3 er alkyl.
5. Polypeptidet ifølge krav 1, hvor R3 er alkenyl.
6. Polypeptidet ifølge krav 1, hvor z er 1.
7. Polypeptidet ifølge krav 1, hvor Ri og R2 hver er methyl.
8. Polypeptidet ifølge krav 7, hvor x er 3 eller 6.
9. Polypeptidet ifølge krav 1, hvor R3 er Cs alkyl eller Cs alkenyl og x er 3:
10. Polypeptidet ifølge krav 1, hvor R3 er Cu alkyl eller Cu alkenyl og x er 6.
11. Polypeptidet ifølge krav 1, hvor R3 er -CH2-CH2-CH2-CH=CH-CH2-CH2-CH2-.
12. Polypeptidet ifølge krav 1, hvor polypeptidet binder til et BCL-2-familie polypeptid.
13. Polypeptidet ifølge krav 1, hvor polypeptidet omfatter et BCL-2-homologi-domæne eller BH3-domæne.
14. Polypeptidet ifølge krav 1, hvor polypeptidet binder til et BH1-, BH2- eller BH3-domæne.
15. Polypeptidet ifølge krav 4 eller ifølge krav 5, hvor R3 er Cs alkyl eller Cu alkyl.
16. Farmaceutisk sammensætning omfattende en forbindelse ifølge et hvilket som helst af kravene 1 til 15, og en farmaceutisk acceptabel bærer, adjuvans eller bærerstof.
DK10195495.6T 2003-11-05 2004-11-05 Alpha-helix peptider egnede til aktivering eller inhibering af celledød DK2332968T3 (da)

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US51784803P 2003-11-05 2003-11-05
US59154804P 2004-07-27 2004-07-27
EP04811198.3A EP1680443B9 (en) 2003-11-05 2004-11-05 Stabilized alpha helical peptides and uses thereof

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DK2332968T3 true DK2332968T3 (da) 2016-08-22

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DK04811198.3T DK1680443T5 (da) 2003-11-05 2004-11-05 Stabiliserede alfa-helix-peptider og anvendelser heraf
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EP (4) EP1997828B1 (da)
JP (5) JP5122142B2 (da)
CN (3) CN1906209A (da)
AU (1) AU2004287884C1 (da)
BR (1) BRPI0416258A (da)
CA (2) CA2830063C (da)
CY (1) CY1114944T1 (da)
DK (2) DK1680443T5 (da)
ES (2) ES2437567T3 (da)
IL (3) IL175152A (da)
PL (2) PL2332968T3 (da)
PT (2) PT2332968T (da)
SI (1) SI1680443T1 (da)
WO (1) WO2005044839A2 (da)
ZA (1) ZA200603565B (da)

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