title: 'Click peptide' using production of monomer Aβ from the O-acyl isopeptide: application to assay system of aggregation inhibitors and cellular cytotoxicity.
abstract: The O-acyl isopeptide of Aβ1-42 (1), possessing an ester bond at the Gly(25)-Ser(26) sequence, is a water-soluble and non-aggregative precursor molecule and is capable of production of monomer Aβ1-42. The SDS-PAGE result showed that the Aβ1-42, produced from 1, adopted monomeric state at first and then self-assembled to oligomer. The oligomeric state was stabilized by nordihydroguaiaretic acid. The Thioflavin-T (ThT) fluorescence intensity derived from Aβ1-42 (generated from 1) was suppressed by various aggregation inhibitors. Finally, 1 could generate Aβ1-42 via the O-to-N acyl migration under cellular medium conditions and the produced Aβ1-42 exhibited cytotoxicity against PC12 cells. These results suggest that the click peptide system, which enables us to predominantly produce monomer Aβ1-42 under physiological conditions, would be adoptable to various biochemical and biophysical experiments including cellular system to investigate the functions of Aβ1-42.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan. ysohma@mb.kyoto-phu.ac.jp
authors.forename: Youhei
authors.initials: Y
authors.lastname: Sohma
authors.forename: Yuta
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Hidehito
authors.initials: H
authors.lastname: Mukai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation / Q000187:drug effects; D057930:Click Chemistry / Q000379:methods; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D015394:Molecular Structure; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D015815:Cell Adhesion Molecules; D010446:Peptide Fragments; D010455:Peptides; C075222:amyloid beta-protein (1-42); C013065:cell aggregation factors