Phosphorus-containing inhibitors of angiotensin-converting enzyme.
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.
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006020:Glycopeptides / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D009943:Organophosphorus Compounds; D010710:Phosphates; C008890:phosphoramidon