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Title: Discovery of a Small-Molecule-Dependent Photolytic Peptide
Authors: Takemoto, Yasushi  kyouindb  KAKEN_id
Mao, Di
Punzalan, Lynn, Louvy
Götze, Sebastian
Sato, Shin-Ichi
Uesugi, Motonari  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-8515-445X (unconfirmed)
Author's alias: 竹本, 靖
佐藤, 慎一
上杉, 志成
Issue Date: 22-Jan-2020
Publisher: American Chemical Society (ACS)
Journal title: Journal of the American Chemical Society
Volume: 142
Issue: 3
Start page: 1142
End page: 1146
Abstract: 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.
Rights: 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(Published Version): 10.1021/jacs.9b09178
PubMed ID: 31899620
Appears in Collections:Journal Articles

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