Highly potent and specific inhibitors of human renin.
We designed aldehyde derivatives of small peptides representing the C-terminal portion of angiotensin I sequence as an inhibitor of human renin. Among compounds that we synthesized, benzyloxycarbonyl (Z)-Phe-His-Leucinal (compound V), Z-Pro-Phe-His-Leucinal (Compound IV) and Z-[3-(1'-naphthyl)Ala]-His-Leucinal (compound VII) markedly inhibited human renin (IC50, 7.5 X 10(-7), 3.2 X 10(-7) and 8.0 X 10(-8) mol/l, respectively). Compound VII was shown to be noncompetitive (Ki = 2.4 X 10(-7) mol/l). It did not inhibit either cathepsin D or pepsin. Compound V had slight or no inhibitory effect at the concentration of 10(-5) mol/l on six animal renins except for monkey and rabbit renins. Results obtained show that these aldehyde compounds are highly selective and species specific inhibitors for human and monkey renins.
D000447:Aldehydes / Q000494:pharmacology*; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D004151:Dipeptides; D004285:Dogs; D006041:Goats; D000882:Haplorhini; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine; D000092502:Renin Inhibitors
D000447:Aldehydes; D000803:Angiotensin I; D004151:Dipeptides; D009842:Oligopeptides; D010446:Peptide Fragments; D000092502:Renin Inhibitors