L-arginine analogs as alternate substrates for nitric oxide synthase

Bioorg Med Chem Lett. 2005 Sep 1;15(17):3934-41. doi: 10.1016/j.bmcl.2005.05.088.


The L-arginine analogs, N(delta)-methyl-L-arginine (deltaMA) and L-canavanine, were used to probe the role of the N delta nitrogen of L-arginine in the reaction catalyzed by nitric oxide synthase (NOS). deltaMA was synthesized and found to be a partial alternate substrate and a weak, reversible inhibitor of NOS with a Ki equal to 1.4 mM. deltaMA undergoes hydroxylation; however, it is not converted further, hence it functions as a partial substrate. L-Canavanine was converted to an L-homoserine presumably via initial hydroxylation and decomposition. The mechanism of this reaction and products of this reaction were not probed further.

MeSH terms

  • Arginine / analogs & derivatives*
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II
  • Structure-Activity Relationship
  • Substrate Specificity


  • Enzyme Inhibitors
  • Arginine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II