2-Iminobiotin is an inhibitor of nitric oxide synthases.
Nitric oxide synthase (NOS, EC 1.14.23) catalyzes the oxidation of the guanidino-nitrogen of L-arginine to form nitric oxide and L-citrulline. 2-Iminobiotin was found to be a reversible inhibitor of murine iNOS and rat n-cNOS with Ki values of 21.8 and 37.5 microM, respectively. The urea and thiourea analogs, biotin and thiobiotin, were not inhibitors of NOS, indicating that the guanidino group of 2-iminobiotin is essential for binding. 2-iminobiotin carboxy derivatives were also inhibitors of iNOS which indicates that the free carboxyl group is not required for binding. 2-Iminobiotin is a novel, potent inhibitor of NO biosynthesis and may be a useful reagent in the understanding of binding-site interactions for this important class of enzymes.
Sup
S J
SJ
Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065.
Green
B G
BG
Grant
S K
SK
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001710:Biotin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D051379:Mice; D019001:Nitric Oxide Synthase; D051381:Rats; D013329:Structure-Activity Relationship
D001710:Biotin; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C028072:2-iminobiotin