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ID: ALA1153920

Journal: Bioorg Med Chem Lett

Title: 4,4-Difluorinated analogues of l-arginine and N(G)-hydroxy-l-arginine as mechanistic probes for nitric oxide synthase.

Authors: Martin NI, Woodward JJ, Winter MB, Marletta MA.

Abstract: 4,4-Difluoro-l-arginine and 4,4-difluoro-N(G)-hydroxy-l-arginine were synthesized and shown to be substrates for the inducible isoform of nitric oxide synthase (iNOS). Binding of both fluorinated analogues to the NOS active site was also investigated using a spectral binding assay employing a heme domain construct of the inducible NOS isoform (iNOS(heme)). 4,4-Difluoro-N(G)-hydroxy-arginine was found to bind at the NOS active site in a unique manner consistent with a model involving ligation of the Fe(III) heme center by the oxygen atom of the N(G)-hydroxy moiety.

CiteXplore: 19230661

DOI: 10.1016/j.bmcl.2009.01.076