論文 - 詳細
| RRC ID | 54841 |
|---|---|
| 著者 | Yamamoto M, Shinoda K, Sasaki D, Kanai M, Sohma Y. |
| タイトル | Design and properties of [Met35(O)]Aβ42-lactam(Asp23/Lys28) possessing a lactam tether as a salt-bridge surrogate. |
| ジャーナル | 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. |
| 巻・号 | 27(5) |
| ページ | 888-893 |
| 公開日 | 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 |
| 引用数 | 1 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |