Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42)

J Org Chem. 2004 Oct 29;69(22):7776-8. doi: 10.1021/jo048922y.

Abstract

The beta-amyloid(1-42) sequence has long been recognized as a challenging target for solid-phase peptide synthesis. We found that the known disaggregating role of Met-35 sulfoxide could be capitalized during stepwise solid-phase assembly of the A beta(1-42) peptide chain to mitigate on-resin peptide chain aggregation, a presumed major source of synthetic difficulties. Furthermore, we demonstrate a hitherto-unreported on-resin reduction of the sulfoxide "aggregation protecting group" to allow for standard cleavage protocols, obviating a separate solution-phase sulfoxide reduction step.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / chemical synthesis*
  • Amyloid beta-Peptides / chemistry
  • Chemistry, Organic / methods*
  • Methionine / analogs & derivatives
  • Methionine / chemistry
  • Oxidation-Reduction
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / chemistry
  • Sulfoxides / chemistry

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Sulfoxides
  • amyloid beta-protein (1-42)
  • Methionine