Synthesis of boronic acid analogs of L-arginine as alternate substrates or inhibitors of nitric oxide synthase.
The asymmetric synthesis of an unprotected alpha-amino boronic acid analog of L-arginine 1a (boroarg-OH. 2 HCl) and its N alpha-acetyl derivative 1b (Ac-boroarg-OH. HCl) is described. These compounds were evaluated as substrates and inhibitors of recombinant nitric oxide synthases (NOS). Boroarg-OH 1a selectively inhibited inducible NOS (IC50 = 50 microM) compared to the neuronal isoform (IC50 = 300 microM).
Lebarbier
C
C
UMR CNRS, Université de Rennes 1, France.
Carreaux
F
F
Carboni
B
B
Boucher
J L
JL
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001897:Boronic Acids; D002956:Citrulline / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008956:Models, Chemical; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D001897:Boronic Acids; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase