Pepstatin analogs as novel renin inhibitors
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-...
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| Veröffentlicht in: | Journal of medicinal chemistry 1986-07, Vol.29 (7), p.1152-1159 |
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| container_end_page | 1159 |
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| container_issue | 7 |
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| container_title | Journal of medicinal chemistry |
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| creator | Guegan, Remy Diaz, Joseph Cazaubon, Catherine Beaumont, Michel Carlet, Claude Clement, Jacques Demarne, Henri Mellet, Michel Richaud, Jean Paul |
| description | 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. |
| doi_str_mv | 10.1021/jm00157a006 |
| format | Article |
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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. 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Med. Chem</addtitle><description>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. 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Med. Chem</addtitle><date>1986-07-01</date><risdate>1986</risdate><volume>29</volume><issue>7</issue><spage>1152</spage><epage>1159</epage><pages>1152-1159</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><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.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>3543358</pmid><doi>10.1021/jm00157a006</doi><tpages>8</tpages></addata></record> |
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| ispartof | Journal of medicinal chemistry, 1986-07, Vol.29 (7), p.1152-1159 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Binding Sites Chemistry Chromatography, Thin Layer Exact sciences and technology Humans Indicators and Reagents Magnetic Resonance Spectroscopy Oligopeptides - chemical synthesis Organic chemistry Pepstatins - chemical synthesis Pepstatins - pharmacology Peptides Preparations and properties Renin - antagonists & inhibitors Renin - blood Structure-Activity Relationship |
| title | Pepstatin analogs as novel renin inhibitors |
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