Biological properties of angiotensin-converting enzyme inhibitor derived from tuna muscle.
A novel inhibitor of angiotensin-converting enzyme (ACE) derived from tuna muscle, Pro-Thr-His-Ile-Lys-Trp-Gly-Asp (tuna AI), was chemically synthesized, and its biological properties were investigated. Synthetic tuna AI was found to be chemically and biologically indistinguishable from the native one. Tuna AI inhibited rabbit lung ACE non-competitively with Ki values of 1.7 and 5.7 microM with substrates, hippuryl-L-histidyl-L-leucine and angiotensin I, respectively. This peptide (5.3 microM) also doubled the effect of bradykinin in the contraction of isolated guinea pig ileum. The peptide did not show zinc chelating activity and carboxypeptidase A inhibitory activity. Thus, tuna AI was found to be a unique ACE inhibitory peptide with non-competitive manner, differing from many naturally occurring peptide ACE-inhibitors.
Kohama
Y
Y
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Oka
H
H
Matsumoto
S
S
Nakagawa
T
T
Miyamoto
T
T
Mimura
T
T
Nagase
Y
Y
Satake
M
M
Takane
T
T
Fujita
T
T
D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D043422:Carboxypeptidases A; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009132:Muscles; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D014413:Tuna; D015032:Zinc / Q000494:pharmacology; D017967:Zinc Compounds
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D009842:Oligopeptides; D017967:Zinc Compounds; C062708:tuna AI; C016837:zinc chloride; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D015032:Zinc; D001920:Bradykinin