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Phomoxanthone A Targets ATP Synthase
Rameez Ali1, Sangram S Parelkar2, Paul R Thompson2
1Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 60 Prescott St., Worcester, MA 01609, USA.
Abstract:
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.
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