Title:
INHIBITORS AND DISASSEMBLERS OF FIBRILLOGENESIS
Document Type and Number:
WIPO Patent Application WO2002074931
Kind Code:
A3
Abstract:
Methods and compositions are presented that inhibit fibril formation and/or bring about disassembly of pre-formed fibrils. Compositions include peptides with short beta-strands with two faces (Figure 1): one that can bind to beta-amyloids through hydrogen bonds, and one which blocks propagation of hydrogen bonding needed to form fibrils. Thus, short congeners of the fibril protein containing N-methyl amino acids or esters are provided for the inhibition of fibril formation ad for the disassembly of preexisting or pre-formed fibrils. Specific aspects address beta-amyloid fibrils; prion mediated fibrils; Huntington protein fibrils. Methods for screening for potential fibril inhibitors and disassemblers, diagnostic analysis and treatments are provided.
Inventors:
GORDON DAVID J (US)
MEREDITH STEPHEN C (US)
MEREDITH STEPHEN C (US)
Application Number:
PCT/US2002/008803
Publication Date:
February 20, 2003
Filing Date:
March 20, 2002
Export Citation:
Assignee:
UNIV CHICAGO (US)
GORDON DAVID J (US)
MEREDITH STEPHEN C (US)
GORDON DAVID J (US)
MEREDITH STEPHEN C (US)
International Classes:
C07K14/47; A61K38/00; (IPC1-7): A61K38/02; A61K38/17; C07K1/113; C07K14/47
Foreign References:
| US6319498B1 | 2001-11-20 |
Other References:
SOTO ET AL.: "The alpha-helical to beta-strand transition in the amino-terminal fragment of the amyloid beta-peptide modulates amyloid formation", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 7, 17 February 1995 (1995-02-17), pages 3063 - 3067, XP001071291
FRASER ET AL.: "Conformation and fibrillogenesis of Alzheimer A-beta peptides with selected substitution of charged residues", J. MOL. BIOL., vol. 244, no. 1, 1994, pages 64 - 73, XP002957211
LYNN ET AL.: "Review: model peptides and the physicochemical approach to beta-amyloids", J. STRUCTURAL BIOLOGY, vol. 130, no. 2-3, June 2000 (2000-06-01), pages 153 - 173, XP002957212
FRASER ET AL.: "Conformation and fibrillogenesis of Alzheimer A-beta peptides with selected substitution of charged residues", J. MOL. BIOL., vol. 244, no. 1, 1994, pages 64 - 73, XP002957211
LYNN ET AL.: "Review: model peptides and the physicochemical approach to beta-amyloids", J. STRUCTURAL BIOLOGY, vol. 130, no. 2-3, June 2000 (2000-06-01), pages 153 - 173, XP002957212
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