176022-34-7Relevant academic research and scientific papers
Transition state analogy of phosphonic acid peptide inhibitors of pepsin
Bartlett, Paul A.,Giangiordano, Mark A.
, p. 3433 - 3438 (2007/10/03)
A series of 11 phosphonate peptide analogs, RO2C-Xaa-Yaa-Phe-{PO2--O}-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P2 position, the K(i) values correlate with the K(m)/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P2-P4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (Ile).
