Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts l-arginine to NG-hydroxy-l-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and l-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N′-hydroxyguanidines (1– ...