Phosphorus-containing inhibitors of angiotensin-converting enzyme

Proc Natl Acad Sci U S A. 1982 Apr;79(7):2176-80. doi: 10.1073/pnas.79.7.2176.

Abstract

Several phosphonamides, phosphoramides, and phosphates having the general structure R-Y-P(O)(OH)-X-CH(CH3)-CO-Pro have been synthesized and tested for inhibition of angiotensin-converting enzyme (dipeptidyl carboxypeptidase; peptidyl-dipeptide hydrolase, EC 3.4.15.1). Inhibition was found to depend on the nature of R, Y, and X such that the maximal effect was observed when X = NH, Y = CH2, and R = phi CH2 (50% inhibition at 7 nM). Substitution of CH2 or O at X and O at Y produced significantly less potent inhibitors. Groups shorter or longer than R = phi CH2 led to less active inhibitors, presumably due to nonoptimal interaction of the side chain with the S1 subsite.

Publication types

  • Comparative Study

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors*
  • Enzyme Inhibitors
  • Glycopeptides / pharmacology*
  • Organophosphorus Compounds / pharmacology*
  • Phosphates / pharmacology
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Enzyme Inhibitors
  • Glycopeptides
  • Organophosphorus Compounds
  • Phosphates
  • phosphoramidon