(A) Conserved substrate autocleavage site of C. difficile TcdB and related bacterial toxins. The toxin CPD cleaves after the highlighted leucine residue.
(B) Focused screen of capped di- and tripeptide covalent TcdB CPD inhibitors. Observed IC50 values were determined using the autocleavage assay for covalent AOMK inhibitors with diverse P2 (left) and P3 (right) residues. These compounds were N-terminally capped with carboxybenzyl (Cbz), acetyl (Ac), or hydroxyphenyl acetyl (Hpa) groups. The dipeptide inhibitor Hpa-SL-AOMK was found to be the most potent compound. Data represents the mean of three experiments ± standard deviation.
See also Figure S1.