N-Hydroxyguanidines oxidation by a N3S copper-complex mimicking the reactivity of Dopamine beta-Hydroxylase.
N-Aryl-N'-hydroxyguanidines are compounds that display interesting pharmacological properties but their chemical reactivity remains poorly investigated. Some of these compounds are substrates for the heme-containing enzymes nitric-oxide synthases (NOS) and act as reducing co-substrates for the copper-containing enzyme Dopamine beta-Hydroxylase (DBH) [P. Slama, J.L. Boucher, M. Réglier, Biochem. Biophys. Res. Commun. 316 (2004) 1081-1087]. DBH catalyses the hydroxylation of the important neurotransmitter dopamine into norepinephrine in the presence of both molecular oxygen and a reducing co-substrate. Although many molecules have been used as co-substrates for DBH, their interaction at the active site of DBH and their role in mechanism are not clearly characterized. In the present paper, we have used a water-soluble copper-N(3)S complex that mimics the Cu(B) site of DBH, and aromatic N-hydroxyguanidines as reducers to address this question. N-Aryl-N'-hydroxyguanidines readily reduced copper(II) to Cu(I) and were oxidized into a nitrosoamidine as previously observed in reactions performed with purified DBH. These data describe for the first time the reactivity of N-aryl-N'-hydroxyguanidines with a water-soluble copper(II) complex and help to understand the interaction of co-substrates with copper at the active site of DBH.
Slama
Patrick
P
Institut des Sciences Moléculaires de Marseille/BiosCiences UMR-CNRS 6263, Campus Scientifique de Saint Jérôme, Université Paul Cézanne, 13397 Marseille, France.
Boucher
Jean-Luc
JL
Réglier
Marius
M
D040761:Biomimetic Materials / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004299:Dopamine beta-Hydroxylase / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry*; D006898:Hydroxylamines; D010084:Oxidation-Reduction
D006146:Guanidines; D006898:Hydroxylamines; D003300:Copper; C029604:hydroxyguanidine; D004299:Dopamine beta-Hydroxylase