Quantitative chemoproteomic profiling of beta lactones in cancer cells

The spongiolactones are marine natural products with an unusual rearranged spongiane skeleton and a fused β-lactone ring. These compounds have potential anticancer properties, but their mode of action has yet to be explored. Here we employ activity-based protein profiling to identify the targets of a more potent spongiolactone derivative (probe 3) in live cancer cells, and compare these to the target profile of a simpler β-lactone (probe 4). Furthermore, we treat K562 cells with probe 3 and perform quantitative proteomic analysis of the global proteome after 24 hrs. Together, these proteomic data provide the first insights into the covalent mechanism of action of this natural product class.