Synthesis of L-thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline: a new class of potent nitric oxide synthase inhibitors.
Nitric oxide synthase catalyzes the NADPH- and O2-dependent conversion of L-arginine to L-citrulline and nitric oxide. L-Thiocitrulline, L-homothiocitrulline, and S-methyl-L-thiocitrulline, novel citrulline analogs, have been synthesized and are shown to be potent inhibitors of both the constitutive brain and the inducible smooth muscle isoforms of nitric oxide synthase. Although many N omega-monosubstituted arginine derivatives inhibit nitric oxide synthase, inhibitory citrulline derivatives have not previously been reported. S-Methyl-L-thiocitrulline is significantly more potent than N omega-methyl-L-arginine, the prototypic nitric oxide synthase inhibitor.
Narayanan
K
K
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
Griffith
O W
OW
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000614:Aminocaproates; D015119:Aminocaproic Acid; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002956:Citrulline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D009130:Muscle, Smooth / Q000201:enzymology; D019001:Nitric Oxide Synthase; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000614:Aminocaproates; C086716:homothiocitrulline; C086715:thiocitrulline; C001352:homocitrulline; D002956:Citrulline; D006418:Heme; D007501:Iron; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D013890:Thiourea; C086717:S-methylthiocitrulline; D015119:Aminocaproic Acid