6-Nitrodopamine and 6-nitronoradrenaline (6-nitronorepinephrine), putative products of the nitric oxide (NO)-dependent nitration of dopamine and noradrenaline, are reported to be reversible, competitive inhibitors of neuronal nitric oxide synthase (nNOS) with Ki values of 45 and 52μM respectively. The nitrocatecholamines inhibited H2O2 production in the absence of l-arginine and tetrahydrobiopterin (BH4) (the IC50 values for 6-nitrodopamine and 6-nitronoradrenaline were 85 and 55μM respectively) but without affecting cytochrome c reduction. The apparent Ki values for nitrocatecholamine inhibition of enzyme activation by BH4 were 18μM for 6-nitrodopamine and 40μM for 6-nitronoradrenaline. Both nitrocatecholamines antagonized the dimerization of nNOS induced by BH4 and by l-arginine, the effect being reversed by BH4 (more than 10μM) and l-arginine (e.g. 100μM). Overall, these results suggest that nitrocatecholamines interfere with nNOS activity by binding to the enzyme in the proximity of the substrate and BH4-binding sites near the haem group.
How did each team member/collaborator contribute to the work?The success of this study relied on am ultidisciplinary approach. Dr. Manini coordinated the activities of at eam made up of chemists, physicists and engineers. In detail, the Manini group investigated the synthesis, spectroscopic characterization and self-assembly behaviour of triazatruxenes;D r. Ricciotti was involved with studying the thermal behaviour and thin film deposition of triazatruxenes; Prof. Crescenzi and Prof. Barone performed the computational studies;D r. Barra and Dr.C assinese performed the morphological and electrical characterization of trazatruxene thin films on FET devices;t he ENEA team performed the OLED device fabrication and characterization.What other topics are you working on at the moment?The core idea that inspires the scientific research carried out by the Manini group is simple, timely,challenging and highly competitive:t ot ranslate the unique physical-chemical properties of man's own natural pigments into the emerging fields of organic (bio)electronics and nanomedicine. The group is involved in:1 )the design and synthesis of opportunely functionalized monomer melanin precursors (both dihydroxyindolic and catecholic) for the production of melanin polymers with tailored functional properties;2 )the production and characterization of melanin-based hybrid materials; 3) the characterization of the semiconducting properties of melanins;4 )the manufacturing of stimuli-responsive melanin-based biointerfaces for tissue engineering applications.Invited for this month'sc over is the group of Dr.P aola Manini from the University of Naples Federico II. The cover picture shows the concept underlying the designo famelanin-inspired electroluminescent material for OLED devices. This article is part of aw ell-structured research project aimed at imitatingN ature'sm ost enigmatic and fascinating functional pigments for the design and synthesis of innovative biomaterialsf or organic electronics applications. Read the full text of the article
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