Lipoprotein Signal Peptidase Inhibitors with Antibiotic Properties Identified through Design of a Robust In Vitro HT Platform (Cell Chemical Biology)

Kitamura et al. developed an FRET-based assay to measure the proteolysis of peptide substrates by E. coli lipoprotein signal peptidase (Lsp). After identifying inhibitors with a high-throughput screen, the authors iteratively optimized lead candidates to generate compounds with IC50 values as low as 99 nM, which prevented bacterial growth.