RRC ID 54841
Author Yamamoto M, Shinoda K, Sasaki D, Kanai M, Sohma Y.
Title Design and properties of [Met35(O)]Aβ42-lactam(Asp23/Lys28) possessing a lactam tether as a salt-bridge surrogate.
Journal Bioorg Med Chem
Abstract A characteristic feature of higher-order structures of amyloid β peptide (Aβ) aggregates observed in Alzheimer disease is the salt-bridge between the side-chains of Asp23 (carboxylate) and Lys28 (ammonium). We synthesized an [Met35(O)]Aβ42 possessing a covalently bound lactam tether as an Asp23/Lys28 salt-bridge surrogate (compound 3). The lactam tether of 3 markedly promoted the formation of stable protofibril-like species that exhibited amyloidogenic properties such as a cross-β-sheet structure and cytotoxicity. This finding is consistent with reports that the Asp23/Lys28 salt-bridge of Aβ42 is transiently formed in aggregation intermediates.
Volume 27(5)
Pages 888-893
Published 2019-3-1
DOI 10.1016/j.bmc.2019.01.038
PII S0968-0896(18)32156-4
PMID 30733085
MeSH Amyloid beta-Peptides / chemistry* Amyloid beta-Peptides / toxicity Animals Lactams / chemistry* Lactams / toxicity Oligopeptides / chemistry* PC12 Cells Peptide Fragments / chemistry* Peptide Fragments / toxicity Protein Conformation, beta-Strand Protein Engineering Protein Multimerization Rats
IF 2.802
Times Cited 1
Human and Animal Cells PC-12(RCB0009)