K-4, a novel inhibitor of angiotensin I converting enzyme produced by Actinomadura spiculosospora.
A novel inhibitor of angiotensin I converting enzyme (ACE), named K-4, was isolated from the culture broth of Actinomadura spiculosospora nov. sp. K-4. The K-4 was an oligopeptide containing L-phenylalanine with (R)-1-amino-2-(4-hydroxyphenyl)ethylphosphonic acid as the C-terminal residue. The compound proved to be a specific and reversible inhibitor of ACE with the inhibition constant (Ki) of 0.18 microM, and inhibited ACE non-competitively by use of hippuryl-L-histidyl-L-leucine (HHL) as a substrate. When administrated intravenously to rats, K-4 inhibited the pressor response to angiotensin I.
D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D004151:Dipeptides; D004789:Enzyme Activation / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; D011480:Protease Inhibitors; C048655:antibiotic K 4; D000803:Angiotensin I