Cyclic (hydroxyphosphinyl)acyl dipeptides: a new class of angiotensin converting enzyme inhibitors.
Conformationally constrained phenylbutyl(hydroxyphosphinyl)acyl dipeptides are potent inhibitors of angiotensin converting enzyme. The activity enhancement obtained by introducing conformational constraint into these molecules is greater than for related sulfhydryl and carboxyl analogs. The results are interpreted in terms of a binding model which optimally positions both zinc binding and hydrophobic groups for active site binding.
Weller
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Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
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D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D007202:Indicators and Reagents; D010456:Peptides, Cyclic; D000803:Angiotensin I; D002216:Captopril