Selection of Peptide Inhibitors of Soluble Aβ1-42 Oligomer Formation by Phage Display

• Published in: Bioscience, biotechnology, and biochemistry Vol. 74; no. 11; pp. 2214 - 2219
• Main Authors: KAWASAKI, Takayasu, ONODERA, Kenji, KAMIJO, Shunsuke
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 23.11.2010; Japan Society for Bioscience Biotechnology and Agrochemistry
• Subjects: amyloid; Biological and medical sciences; fibrils; Fundamental and applied biological sciences. Psychology; phage display; soluble oligomers; Phage display; Peptides; Selection; soluble oligomers; Amyloid; Inhibitor; Oligomer; fibrils
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.100388

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 .