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

Abstract

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of different biological processes and are implicated in several diseases. Here, we report 4-oxo-β-lactams as a novel scaffold for inhibition of rhomboids. We here 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.