title: Pepstatin analogues as novel renin inhibitors.
abstract: Pepstatin analogues corresponding to the general formula A-X-Y-Sta-Ala-Sta-R were synthesized in solution phase. Various changes in the nature of the A, X, and Y groups were made to improve the inhibitory potency against human plasma renin activity. The results were interpreted by use of the active-site model based on the sequence of human angiotensinogen. The tert-butyloxycarbonyl group and the isovaleryl group were found to be the most effective acyl groups (A). The analogues having a Phe residue in place of Val1 (X) and His or amino acid with an aliphatic side chain such as norleucine or norvaline in the Y position showed the highest inhibition of human plasma renin activity with IC50 values of about 10(-8)M. Esterification or amidification of the carboxyl group of the C-terminal statine did not change the inhibitory potency. The selectivity for rat, dog, pig, and monkey plasma renin of the most interesting compounds was studied.
mesh_terms: D001665:Binding Sites; D002855:Chromatography, Thin Layer; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis*; D010436:Pepstatins / Q000138:chemical synthesis* / Q000494:pharmacology; D012083:Renin / Q000097:blood; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D007202:Indicators and Reagents; D009842:Oligopeptides; D010436:Pepstatins; D012083:Renin; D000092502:Renin Inhibitors