Synthesis and evaluation of omega-borono-alpha-amino acids as active-site probes of arginase and nitric oxide synthases

Enantiomerically pure omega-borono-alpha-amino acids of various chain lengt hs have been synthesized according to a general methodology involving conde nsation of alkenyl and alkynyl bromides with Ni-II complex of the Schiff ba se derived from glycine and (S)-2-[N'-(N-benzylprolyl)amino]benzophenone, h ydroboration of the intermediate omega-unsaturated alpha-amino acids with d iisopinocampheylborane, and oxidation with acetaldehyde. Some of these comp ounds act as potent inhibitors of rat liver and murine macrophage arginases , demonstrating that distance between the B(OH)(2) and alpha-amino acid gro ups is a key determinant for their interaction with arginase. In contrast, they are without effect on neuronal and inducible NO synthases.