Inhibitors of beta-amyloid formation based on the beta-secretase cleavage site

Biochem Biophys Res Commun. 2000 Feb 5;268(1):133-5. doi: 10.1006/bbrc.2000.2098.

Abstract

A series of inhibitors of beta-amyloid formation have been developed based on the beta-secretase cleavage site (VNL-DA) of the Swedish mutant Amyloid Precursor Protein. A simple tripeptide aldehyde was found to be the most potent (IC(50) = 700 nM) in the series displaying an inhibitory profile which is different from reported inhibitors of beta-amyloid formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Aldehydes / pharmacology
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / chemistry
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / metabolism*
  • Binding Sites
  • COS Cells
  • Cell Line
  • Drug Design
  • Endopeptidases
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Protein Processing, Post-Translational / drug effects
  • Structure-Activity Relationship

Substances

  • Aldehydes
  • Amyloid beta-Peptides
  • Enzyme Inhibitors
  • Oligopeptides
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Aspartic Acid Endopeptidases
  • BACE2 protein, human
  • BACE1 protein, human