alpha-Methylproline-containing renin inhibitory peptides: in vivo evaluation in an anesthetized, ganglion-blocked, hog renin infused rat model.
A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor of human plasma renin with an IC50 value of 1.8 nM. This peptide was shown not to be degraded in vitro by chymotrypsin, elastase, pepsin, and a rat liver homogenate preparation. It is also a potent inhibitor of hog renin with an IC50 value of 1.6 nM and was shown to elicit in vivo activity and cause dose-dependent hypotensive responses when given intravenously to anesthetized ganglion-blocked, hog renin infused rats.
D000595:Amino Acid Sequence; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D013552:Swine; D000092502:Renin Inhibitors
D007202:Indicators and Reagents; D009842:Oligopeptides; D011392:Proline; D012083:Renin; D000092502:Renin Inhibitors; C051624:2-methylproline; C027509:renin inhibitory peptide