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タイトル: | Discovery of a Small-Molecule-Dependent Photolytic Peptide |
著者: | Takemoto, Yasushi Mao, Di Punzalan, Lynn, Louvy Götze, Sebastian Sato, Shin-Ichi Uesugi, Motonari https://orcid.org/0000-0002-8515-445X (unconfirmed) |
著者名の別形: | 竹本, 靖 佐藤, 慎一 上杉, 志成 |
発行日: | 22-Jan-2020 |
出版者: | American Chemical Society (ACS) |
誌名: | Journal of the American Chemical Society |
巻: | 142 |
号: | 3 |
開始ページ: | 1142 |
終了ページ: | 1146 |
抄録: | We accidentally found that YM-53601, a known small-molecule inhibitor of squalene synthase (SQS), selectively depletes SQS from mammalian cells upon UV irradiation. Further analyses indicated that the photodepletion of SQS requires its short peptide segment located at the COOH terminus. Remarkably, when the 27 amino acid peptide was fused to green fluorescent protein or unrelated proteins at either the NH2 or COOH terminus, such fusion proteins were selectively depleted when the cells were treated with both YM-53601 and UV exposure. Product analysis and electron spin resonance experiments suggested that the UV irradiation promotes homolytic C-O bond cleavage of the aryl ether group in YM-53601. It is likely that the radical species generated from UV-activated YM-53601 abstract hydrogen atoms from the SQS peptide, leading to the photolysis of the entire protein. The pair of the SQS peptide and YM-53601 discovered in the present study paves the way for the design of a new small-molecule-controlled optogenetic tool. |
著作権等: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.9b09178. The full-text file will be made open to the public on 3 January 2021 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/246190 |
DOI(出版社版): | 10.1021/jacs.9b09178 |
PubMed ID: | 31899620 |
出現コレクション: | 学術雑誌掲載論文等 |
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