國家衛生研究院 NHRI:Item 3990099045/15174
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    題名: Marine diterpenoid targets STING palmitoylation in mammalian cells
    作者: Hsiao, WC;Niu, GH;Lo, CF;Wang, JY;Chi, YH;Huang, WC;Tung, CW;Sung, PJ;Tsou, LK;Zhang, MM
    貢獻者: Institute of Molecular and Genomic Medicine;Institute of Biotechnology and Pharmaceutical Research
    摘要: Natural products are important sources of therapeutic agents and useful drug discovery tools. The fused macrocycles and multiple stereocenters of briarane-type diterpenoids pose a major challenge to total synthesis and efforts to characterize their biological activities. Harnessing a scalable source of excavatolide B (excB) from cultured soft coral Briareum stechei, we generated analogs by late-stage diversification and performed structure-activity analysis, which was critical for the development of functional excB probes. We further used these probes in a chemoproteomic strategy to identify Stimulator of Interferon Genes (STING) as a direct target of excB in mammalian cells. We showed that the epoxylactone warhead of excB is required to covalently engage STING at its membrane-proximal Cys91, inhibiting STING palmitoylation and signaling. This study reveals a possible mechanism-of-action of excB, and expands the repertoire of covalent STING inhibitors.
    日期: 2023-07-18
    關聯: Communications Chemistry. 2023 Jul 18;6:Article number 153.
    Link to: http://dx.doi.org/10.1038/s42004-023-00956-9
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2399-3669&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001030811000002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85165264642
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