Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures

J Am Chem Soc. 2010 Dec 22;132(50):17655-7. doi: 10.1021/ja106291e. Epub 2010 Nov 24.

Abstract

Alzheimer's disease (AD) is characterized by the self-assembly of amyloid beta (Aβ) peptides. Recent models implicate some of the earliest Aβ oligomers, such as trimers and tetramers, in disease. However, the roles of these structures remain uncertain, in part, because selective probes of their formation are not available. Toward that goal, we generated bivalent versions of the known Aβ ligand, the pentapeptide KLVFF. We found that compounds containing sufficiently long linkers (∼19 to 24 Å) recognized primarily Aβ trimers and tetramers, with little binding to either monomer or higher order structures. These compounds might be useful probes for early Aβ oligomers.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics*
  • Ligands
  • Molecular Probes* / chemistry
  • Molecular Probes* / genetics
  • Molecular Structure
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics*

Substances

  • Amyloid beta-Peptides
  • Ligands
  • Molecular Probes
  • Peptide Fragments
  • amyloid beta-protein (16-20)