Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation

Biochem Biophys Res Commun. 1996 Sep 24;226(3):672-80. doi: 10.1006/bbrc.1996.1413.

Abstract

Amyloid beta-peptide (A beta) is a major fibrillar component of neuritic plaques in Alzheimer's disease (AD) brains and is related to the pathogenesis of the disease. We hypothesized that amyloid formation could be inhibited by peptides homologous to A beta (position 17-21) with a similar degree of hydrophobicity, but with a very low propensity to adopt a beta-sheet conformation by incorporating proline residues (anti-beta-sheet peptides or beta-sheet inhibitors). An 11-residue peptide with these characteristics binds to A beta, inhibits A beta fibril formation and partially disaggregates preformed fibrils in vitro. Shorter anti-beta-sheet peptides and analogs containing D-amino acids are also able to inhibit A beta fibrillogenesis. The latter are more resistant to proteolytic degradation and may serve as a starting point to design more efficient peptides derivatives to inhibit amyloidogenesis in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / ultrastructure
  • Amyloidosis*
  • Humans
  • Kinetics
  • Microscopy, Electron
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Probability
  • Protein Structure, Secondary* / drug effects
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments