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

Intramembrane serine proteases (rhomboid proteases) are involved in a variety of biological processes and are implicated in several diseases. Here, we report 4-oxo-beta-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 rhomboidlactam complex. 4-Oxo-beta-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.