Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogs

• DOI: 10.1021/jo00313a012
• Publication Date: 2005-03-12T03:43:50Z
• Authors: Paul A. Bartlett; John E. Hanson; Peter P. Giannousis
• Keywords: 01 natural sciences; 0104 chemical sciences

The substitution of a phosphonate ester moiety for the scissile peptide linkage in oligopeptide substrates of pepsin and penicillopepsin leads to potent inhibitors of these enzymes. For the most part, conventional binding kinetics were observed for these phosphonate inhibitors. The pH dependence of the binding affinity of the latter compound suggests that protonation of the active-site carboxylate, is required for binding