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Identification of a Covalent Importin-5 Inhibitor, Goyazensolide, from a Collective Synthesis of Furanoheliangolides

Published inACS Central Science, vol. 7, no. 6, p. 954-962
Publication date2021
Abstract

Sesquiterpenes are a rich source of covalent inhibitors with a long history in traditional medicine and include several important therapeutics and tool compounds. Herein, we report the total synthesis of 16 sesquiterpene lactones via a build/couple/pair strategy, including goyasensolide. Using an alkyne-tagged cellular probe and proteomics analysis, we discovered that goyazensolide selectively targets the oncoprotein importin-5 (IPO5) for covalent engagement. We further demonstrate that goyazensolide inhibits the translocation of RASAL-2, a cargo of IPO5, into the nucleus and perturbs the binding between IPO5 and two specific viral nuclear localization sequences.

Citation (ISO format)
LIU, Weilong et al. Identification of a Covalent Importin-5 Inhibitor, Goyazensolide, from a Collective Synthesis of Furanoheliangolides. In: ACS Central Science, 2021, vol. 7, n° 6, p. 954–962. doi: 10.1021/acscentsci.1c00056
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ISSN of the journal2374-7951
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Technical informations

Creation06/24/2021 6:07:00 PM
First validation06/24/2021 6:07:00 PM
Update time03/16/2023 12:48:29 AM
Status update03/16/2023 12:48:28 AM
Last indexation02/12/2024 1:27:51 PM
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