Emily Ho Rose Hills
The Anticancer Mechanism of Dankastatin B with Mitochondrial Proteins
Current protein therapeutic methods can only target less than 15% of human proteins, leaving many disease-causing proteins untouched. Natural products produced by plants and fungi are complex small molecules that have the potential to bind to these proteins and be repurposed as drug scaffolds. The gymnastatin family of natural products produced by the fungus Gymnascella dankaliensis has antiproliferative effects on triple-negative breast cancer cells. Dankastatin B, the most potent gymnastatin against cancer cell viability, selectively binds to the mitochondrial membrane proteins VDAC3 and VDAC2, and causes cancer cells to die through intrinsic apoptosis. We hypothesize that Dankastatin B could be causing the VDAC proteins to oligomerize, which initiates apoptosis. I hope to show oligomerization of the VDAC proteins via pulldown assays and determine which components of the molecule bind to the cysteines of its target proteins via structure-activity relationship (SAR) studies.
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