4-Oxo-β-Lactams as Novel Inhibitors for Rhomboid Proteases

Abstract

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of biological processes and are implicated in several diseases. Here, we report 4-oxo-β-lactams as a novel scaffold for inhibition of rhomboids. We show that they covalently react with the active site and that the covalent bond is sufficiently stable for detection of the covalent rhomboid-lactam complex. 4-Oxo-β-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.

Keywords: activity-based protein profiling; beta-lactams; covalent inhibitors; intramembrane proteases; protease inhibitors.