139299-32-4Relevant articles and documents
A General Procedure for Synthesis of NG-Alkyl, and NG-Aryl-L-Arginines as Potential Nitric Oxide Synthase Inhibitors
Chen, Bor-Cherng,Shiu, Shi,Yang, Ding-Yah
, p. 549 - 553 (2007/10/03)
A general procedure for the synthesis of NG-alkyl, and NG-aryl-L-arginines with relatively high overall yield is reported. The key step involved the coupling of protected L-ornithine 4 with isothiourea 7 to give the fully protected NG-aryl-L-arginine derivative 8. Subsequent deprotection of 8 in acidic condition provided the final target compound 9 with an overall yield of more than 80%.
NG-Allyl- and NG-Cyclopropyl-L-arginine: Two Novel Inhibitors of Macrophage Nitric Oxide Synthase
Olken, Norman M.,Marletta, Michael A.
, p. 1137 - 1144 (2007/10/02)
NG-Methyl-L-arginine has recently been shown to inactivate the inducible murine macrophage nitric oxide (.NO) synthase (Olken, N.M.; Rusche, K.M.; Richards, M.K.; Marletta, M.A.Biochem.Biophys.Res.Commun. 1991, 177, 828-833).NG-Allyl-L-arginine and NG-cyclopropyl-L-arginine were synthesized as potential mechanism-based enzyme inhibitors to exploit the chemistry presumed to occur at the active site.NG-Cyclopropyl-L-arginine was found to be a potent reversible inhibitor with a Ki = 7.7 μM.NG-Allyl-L-arginine was found to be both a potent reversible (Ki = 2.1 μM) and irreversible inhibitor of the enzyme.The irreversible inhibition demonstrated pseudo-first-order inactivation kinetics with kinact = 0.026 min-1 and Ki = 3.4 μM.Stereospecific protection of the inactivation was afforded by L-arginine, and saturability of the inactivation rate was observed.Our studies indicate that both reversible and irreversible inhibition of the inducible .NO synthase can be achieved with relatively simple modifications of the substrate L-arginine.
