Inhibition of Abeta42 aggregation using peptides selected from combinatorial libraries

J Pept Sci. 2009 Aug;15(8):499-503. doi: 10.1002/psc.1150.

Abstract

Increasing evidence suggests that the aggregation of the small peptide Abeta42 plays an important role in the development of Alzheimer's disease. Inhibiting the initial aggregation of Abeta42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Abeta42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Abeta42 fibers.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / chemistry
  • Benzothiazoles
  • Drug Evaluation, Preclinical
  • Molecular Sequence Data
  • Peptide Library*
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Thiazoles / chemistry

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Peptide Library
  • Peptides
  • Thiazoles
  • thioflavin T