Work

Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone

Year: 2014

Type: article

Abstract: 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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja412431g

Authors: Neil J. Lajkiewicz, Armand B. Cognetta, Micah J. Niphakis, Benjamin F. Cravatt, John A. Porco

Institutions: Boston University, Scripps Research Institute

Language: English

Topic: Bioactive natural compounds

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500