Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone
Lajkiewicz, Neil J.
Cognetta, Armand B.
Niphakis, Micah J.
Cravatt, Benjamin F.
Porco, John A.
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CitationNeil J Lajkiewicz, Armand B Cognetta, Micah J Niphakis, Benjamin F Cravatt, John A Porco. 2014. "Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone.." J Am Chem Soc, Volume 136, Issue 6, pp. 2659 - 2664.
Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.