4-Oxo-ß-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-ß-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-ß-lactams may therefore find future use as both inhibitors and activity-based probes for rhomboid proteases.