Superoxide dismutase designations

Structure-Activity Studies and the Design of Synthetic Superoxide Dismutase (SOD) Mimetics as Therapeutics... 

Several reports indicate the involvement of superoxide in the mediation of tolerance [67-69]. Based on these reports, a bifunctional superoxide dismutase-mimic NO donor was designed by Haj-Yehia s group [70]. The nitrate ester was incorporated into a nitroxide such as 3-hydroxymethyl-2,2,5,5-tetramethyl-l-pyrroHdinyloxy (HMP) by its conversion into 3-nitratomethyl-PROXYL (NMP) (Scheme 1.7). HMP is a stable, metal-independent, low-molecular weight SOD-mimic with excellent cell-permeability. So NMP is the first compound that can simultaneously generate NO and destroy superoxide. This may lead to novel nontolerance-inducing nitrovasodila-tors. 

Riley, D.P. Rational design of synthetic enzymes and their potential utility as human pharmaceuticals development of manganese(II)-based superoxide dismutase mimics. Adv. Supramol. Chem. 2000, 6, 217-244. 

Riley, D.P., Henke, S.L, Lennon, P.J., Aston, K. Computer-aided design (CAD) of synzymes use of molecular mechanics (MM) for the rational design of superoxide dismutase mimics. Inorg. Chem. 1999, 38(8), 1908-1917. 

The demonstration that PMNs formed O2- in the respiratory burst necessitated the consideration of all the species which result when dioxygen is reduced one electron at a time (Fig. 1). Superoxide, the result of the reduction of dioxygen by one electron, appears to act mainly as a mild reductant in aqueous solutions. But when it coexists with H2O2, its spontaneous dismutation product, O can initiate a number of potentially injurious events [reviewed by Fridovich The primary means by which cells deal with superoxide anions appears to be through the catalysis of their dismutation by a family of metalloenzymes collectively designated superoxide dismutases. 

ED Getzoff, DE Cabelli, CL Fisher, HE Parge, MS Viezzoli, L Banci, RA Hallewell. Faster superoxide dismutase mutants designed by enhancing electrostatic guidance. Nature 358 347-351, 1992. 

A number of copper requiring enzymes are located at the cell surface or are exported into the extracellular milieu. Examples of such secretory Cu-enzymes include copper requiring ferroxidases that fimction in iron transport (e g. ceruloplasmin, CP), enzymes for neurotransmission (peptidyl amidating enzyme and dopamine hydroxylase), an extracellular superoxide dismutase (SOD) that fimctions in antioxidant defense and enzymes for formation of connective tissue (lysyl oxidase), and pigments (tyrosinase) (reviewed in ). En route to their designated location, each of these enzymes passes through a specialized compartment of the late Golgi where copper insertion takes place. 

RATIONAL DESIGN OF SYNTHETIC ENZYMES AND THEIR POTENTIAL UTILITY AS HUMAN PHARMACEUTICALS DEVELOPMENT OF MANGANESEdD-BASED SUPEROXIDE DISMUTASE MIMICS Dennis P. Riley... 

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