Literature

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.

DOI： 10.1016/j.bmcl.2009.01.076

4,4-Difluorinated analogues of l-arginine and NG-hydroxy-l-arginine as mechanistic probes for nitric oxide synthase

Bioorganic & Medicinal Chemistry Letters 2009.0

Isoform-Selective Substrates of Nitric Oxide Synthase

Journal of Medicinal Chemistry 2003.0

Conformationally restricted arginine analogues as inhibitors of human nitric oxide synthase

Bioorganic & Medicinal Chemistry Letters 1997.0

NG-Aminoguanidines from Primary Amines and the Preparation of Nitric Oxide Synthase Inhibitors

Journal of Medicinal Chemistry 2008.0

l-Arginine analogs as alternate substrates for nitric oxide synthase

Bioorganic & Medicinal Chemistry Letters 2005.0

Oxidation of Nω-Hydroxyarginine Analogues by NO-Synthase: The Simple, Non Amino Acid N-Butyl N‘-Hydroxyguanidine Is Almost as Efficient an NO Precursor as Nω-Hydroxyarginine