ダウンロード数: 61
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
acsmedchemlett.1c00591.pdf | 1.16 MB | Adobe PDF | 見る/開く |
完全メタデータレコード
DCフィールド | 値 | 言語 |
---|---|---|
dc.contributor.author | Kitamura, Takashi | en |
dc.contributor.author | Suzuki, Rikito | en |
dc.contributor.author | Inuki, Shinsuke | en |
dc.contributor.author | Ohno, Hiroaki | en |
dc.contributor.author | McPhail, Kerry L. | en |
dc.contributor.author | Oishi, Shinya | en |
dc.contributor.alternative | 喜多村, 隆志 | ja |
dc.contributor.alternative | 鈴木, 力斗 | ja |
dc.contributor.alternative | 井貫, 晋輔 | ja |
dc.contributor.alternative | 大野, 浩章 | ja |
dc.contributor.alternative | 大石, 真也 | ja |
dc.date.accessioned | 2022-05-25T23:49:53Z | - |
dc.date.available | 2022-05-25T23:49:53Z | - |
dc.date.issued | 2022-01 | - |
dc.identifier.uri | http://hdl.handle.net/2433/274023 | - |
dc.description.abstract | Coibamide A, a cyclic depsipeptide isolated from a Panamanian marine cyanobacterium, shows potent cytotoxic activity via the inhibition of the Sec61 translocon. We designed a coibamide A mimetic in which the ester linkage between MeThr and d-MeAla in coibamide A was replaced with an alkyl linker to provide a stable macrocyclic scaffold possessing a MeLys(Me) residue. Taking advantage of a facile solid-phase synthetic approach, an structure–activity relationship (SAR) study of the newly designed macrocyclic structure was performed, with a focus on altering the pattern of N-methyl substitution and amino acid configurations. Overall, the simplified macrocyclic scaffold with an alkyl linker resulted in a significantly reduced cytotoxicity. Instead, more potent coibamide A derivatives with a β-(4-biphenylyl)alanine (Bph) group were identified after the optimization of the Tyr(Me) position in the original macrocyclic scaffold of coibamide A based on the characteristic apratoxin A substructures. The similar SAR between coibamide A and apratoxin A suggests that the binding site of the Tyr(Me) side chain at the luminal end of Sec61α may be shared. | en |
dc.language.iso | eng | - |
dc.publisher | American Chemical Society (ACS) | en |
dc.rights | © 2021 The Authors. Published by American Chemical Society | en |
dc.rights | This article is licensed under the Creative Commons Attribution 4.0 International License. | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | apratoxin A | en |
dc.subject | biphenylylalanine | en |
dc.subject | coibamide A | en |
dc.subject | macrocyclic peptide | en |
dc.subject | Sec61 | en |
dc.subject | translocon | en |
dc.title | Design of Coibamide A Mimetics with Improved Cellular Bioactivity | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | ACS Medicinal Chemistry Letters | en |
dc.identifier.volume | 13 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 105 | - |
dc.identifier.epage | 110 | - |
dc.relation.doi | 10.1021/acsmedchemlett.1c00591 | - |
dc.textversion | publisher | - |
dc.identifier.pmid | 35059129 | - |
dcterms.accessRights | open access | - |
dc.identifier.pissn | 1948-5875 | - |
出現コレクション: | 学術雑誌掲載論文等 |
このアイテムは次のライセンスが設定されています: クリエイティブ・コモンズ・ライセンス