Inhibition of Cu-amyloid-β by using bifunctional peptides with β-sheet breaker and chelator moieties

Chemistry. 2012 Apr 16;18(16):4836-9. doi: 10.1002/chem.201103546. Epub 2012 Mar 15.

Abstract

Breaking the mold: Inhibition of toxic amyloid-β (Aβ) aggregates and disruption of Cu-Aβ with subsequent redox-silencing of Cu have been considered promising strategies against Alzheimer's disease. The design and proof of concept of simple peptides containing a Cu-chelating/redox-silencing unit and an Aβ-aggregation inhibition unit (β-sheet breaker) is described (see scheme).

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amyloid / antagonists & inhibitors*
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacology
  • Copper / chemistry*
  • Copper / pharmacology
  • Models, Molecular
  • Molecular Sequence Data
  • Oxidation-Reduction
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Secondary

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Chelating Agents
  • Peptide Fragments
  • Copper