Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 60 Prescott St., Worcester, MA 01609, USA.
Department of Chemical Biology, University of Massachusetts Medical School, 364 Plantation St., Wocester, MA 01605, USA.
Chemistry. 2022 Dec 15;28(70):e202202397. doi: 10.1002/chem.202202397. Epub 2022 Oct 25.
Phomoxanthone A is a naturally occurring molecule and a powerful anti-cancer agent, although its mechanism of action is unknown. To facilitate the determination of its biological target(s), we used affinity-based labelling using a phomoxanthone A probe. Labelled proteins were pulled down, subjected to chemoproteomics analysis using LC-MS/MS and ATP synthase was identified as a likely target. Mitochondrial ATP synthase was validated in cultured cells lysates and in live intact cells. Our studies show sixty percent inhibition of ATP synthase by 260 μM phomoxanthone A.
黄皮醌 A 是一种天然存在的分子，也是一种强大的抗癌剂，尽管其作用机制尚不清楚。为了方便确定其生物靶标，我们使用了基于亲和力的标记方法，使用黄皮醌 A 探针。标记的蛋白质被拉下，用 LC-MS/MS 进行化学蛋白质组学分析，鉴定出 ATP 合酶可能是一个靶标。线粒体 ATP 合酶在培养细胞裂解物和活完整细胞中得到了验证。我们的研究表明，黄皮醌 A 对 ATP 合酶的抑制率为 60%，抑制浓度为 260 μM。
