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

Biochem Biophys Res Commun. 2010 Jul 2;397(3):509-12. doi: 10.1016/j.bbrc.2010.05.144. Epub 2010 May 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / pharmacology*
  • Benzothiazoles
  • Circular Dichroism
  • Fluorescent Dyes / chemistry
  • Humans
  • Microscopy, Atomic Force
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Thiazoles / chemistry

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Fluorescent Dyes
  • Peptide Fragments
  • Peptides
  • Thiazoles
  • amyloid beta-protein (1-40)
  • amyloid-beta(40-1)-Gly8-1-40 peptide
  • thioflavin T