Marine derived natural product inhibits a molecular machine

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Professor Patrick Harran’s group and collaborators have discovered how the marine natural product callyspongiolide kills cancer cells. 

The discovery was the result of a collaboration between the Harran group and Professor Jared Rutter’s group at the University of Utah/HHMI and Professor Karlett Parra’s group at the University of New Mexico. They reported on their discovery in a recent paper titled “Callyspongiolide Is a Potent Inhibitor of the Vacuolar ATPase” published in the ACS’s Journal of Natural Products on November 5, 2020.  

At UCLA in 2017, Harran chemistry graduate student Liubo Li, along with former visiting scholar Corentin Rumo (University of Basil) and former postdoctoral fellow Francesco Manoni (now a scientist at Amgen), synthesized callyspongiolide. Exploiting their synthetic material, Harran joined forces with Rutter and Parra to explore its biological mechanism of action.

Harran Research ImageUsing yeast as a model organism, they discovered that callyspongiolide is a hyper-potent inhibitor of the vacuolar H+ ATPase. The VATPase is a large, multi-subunit molecular machine that acidifies intracellular compartments and plays a key role in cellular homeostasis. Inhibitors of VATPase have potential as cancer therapeutics and as novel, broad spectrum anti-viral agents. 

For further information, contact Professor Patrick Harran,

Penny Jennings, UCLA Department of Chemistry & Biochemistry,