Potential lead for an Alzheimer drug: a peptide that blocks intermolecular interaction and amyloid beta protein-induced cytotoxicity

J Med Chem. 2006 Aug 10;49(16):4813-7. doi: 10.1021/jm050718v.

Abstract

A peptide chAbeta30-16 (15-mer; CTFVRTHIFCKEHQF) was designed to bind to a region encompassing the entire polymerization-related (16KLVFF20) and part of the polymerization and toxicity-related (25GSNKGAIIGLM35) regions of amyloid beta-protein, Abeta1-42 by a hydropathic complementary approach. This peptide efficiently binds to Abeta and blocks intermolecular interaction and the formation of Abeta aggregates. In addition, the peptide neutralizes the cell toxicity of Abeta fibrils. The chAbeta30-16 peptide or its derivatives may be a starting point for the future development of drugs that prevent the neurotoxicity and deposition of Abeta in the brain of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Molecular Sequence Data
  • Nootropic Agents / chemical synthesis*
  • Nootropic Agents / chemistry
  • Nootropic Agents / pharmacology
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Peptides / pharmacology
  • Protein Binding
  • Rats
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Nootropic Agents
  • Peptides
  • chAbeta30-16 peptide