Abstract
Abeta peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Abeta(1-40) fibrillization as a tandem dimeric construct consisting of Abeta(40-1) (reverse sequence) linked to Abeta(1-40) via an eight residue glycine linker. At molar ratios of the tandem peptide to Abeta(1-40) of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism*
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / chemistry
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / pharmacology*
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Benzothiazoles
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Circular Dichroism
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Fluorescent Dyes / chemistry
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Humans
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Microscopy, Atomic Force
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Peptide Fragments / antagonists & inhibitors*
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Peptides / chemistry
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Peptides / pharmacology*
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Thiazoles / chemistry
Substances
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Amyloid beta-Peptides
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Benzothiazoles
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Fluorescent Dyes
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Peptide Fragments
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Peptides
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Thiazoles
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amyloid beta-protein (1-40)
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amyloid-beta(40-1)-Gly8-1-40 peptide
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thioflavin T