title: Structure and activity of NO synthase inhibitors specific to the L-arginine binding site.
abstract: Synthesis of compounds containing a fragment similar to the guanidine group of L-arginine, which is a substrate of nitric oxide synthase (NOS), is the main direction in creating NOS inhibitors. The inhibitory effect of such compounds is caused not only by their competition with the substrate for the L-arginine-binding site and/or oxidizing center of the enzyme (heme) but also by interaction with peptide motifs of the enzyme that influence its dimerization, affinity for cofactors, and interaction with associated proteins. Structures, activities, and relative in vitro and in vivo specificities of various NOS inhibitors (amino acid and non-amino acid) with linear or cyclic structure and containing guanidine, amidine, or isothiuronium group are considered. These properties are mainly analyzed by comparison with effects of the inhibitors on the inducible NOS.
authors.affiliation: Medical Radiological Research Center, Russian Academy of Medical Sciences, ul. Koroleva 4, Obninsk 249036, Russia. pros@mrrc.obninsk.ru
authors.forename: S Ya
authors.initials: SY
authors.lastname: Proskuryakov
authors.forename: A G
authors.initials: AG
authors.lastname: Konoplyannikov
authors.forename: V G
authors.initials: VG
authors.lastname: Skvortsov
authors.forename: A A
authors.initials: AA
authors.lastname: Mandrugin
authors.forename: V M
authors.initials: VM
authors.lastname: Fedoseev
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001665:Binding Sites; D003067:Coenzymes; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D003067:Coenzymes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D001120:Arginine; D019001:Nitric Oxide Synthase