Synthesis of the L-arginine congener L-indospicine and evaluation of its interaction with nitric oxide synthase

L-Indospicine (Ind), a natural product amino acid analog of L-arginine, was synthesized from L-glutamic acid 2 in nine steps and 29% overall yield. Ind was evaluated as an alternative substrate or inhibitor of two nitric oxide synthase (NOS) isozymes. Ind did not act as either an alternative substrate or inhibitor of either NOS isozyme and these results were interpreted based on a recent model for substrate and inhibitor binding to the active site of NOS.