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alpha-Methylproline-containing renin inhibitory peptides: in vivo evaluation in an anesthetized, ganglion-blocked, hog renin infused rat model.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Thaisrivongs S,Pals DT,Lawson JA,Turner SR,Harris DW

doi

10.1021/jm00386a016

subject

Has Abstract

pub_date

1987-03-01 00:00:00

pages

536-41

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

30

pub_type

杂志文章

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