Selection of peptide inhibitors of soluble Aβ(1-42) oligomer formation by phage display

Biosci Biotechnol Biochem. 2010;74(11):2214-9. doi: 10.1271/bbb.100388. Epub 2010 Nov 7.

Abstract

There have been many reports suggesting that soluble oligomers of amyloid β (Aβ) are neurotoxins causing Alzheimer's disease (AD). Although inhibition of the soluble oligomerization of Aβ is considered to be effective in the treatment of AD, almost all peptide inhibitors have been designed from the β-sheet structure (H14-D23) of Aβ(1-42). To obtain more potent peptides than the known inhibitors of the soluble-oligomer formation of Aβ(1-42), we performed random screening by phage display. After fifth-round panning of a hepta-peptide library against soluble Aβ(1-42), novel peptides containing arginine residues were enriched. These peptides were found to suppress specifically 37/48 kDa oligomer formation and to keep the monomeric form of Aβ(1-42) even after 24 h of incubation, as disclosed by SDS-PAGE and size-exclusion chromatography. Thus we succeeded in acquiring novel efficient peptides for inhibition of soluble 37/48 kDa oligomer formation of Aβ(1-42).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Library*
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Protein Multimerization / drug effects
  • Solubility

Substances

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