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Substoichiometric inhibition of Abeta(1-40) aggregation by a tandem Abeta(40-1-Gly8-1-40) peptide.

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.

SUBMITTER: Mustafi SM

PROVIDER: S-EPMC2897963 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Substoichiometric inhibition of Abeta(1-40) aggregation by a tandem Abeta(40-1-Gly8-1-40) peptide.

Mustafi Sourajit M SM Garai Kanchan K Crick Scott L SL Baban Berevan B Frieden Carl C

Biochemical and biophysical research communications 20100531 3

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 measu ...[more]

PMID: 20515649

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