Biologically active metal-independent superoxide dismutase mimics

• Published in: Biochemistry (Easton) Vol. 29; no. 11; pp. 2802 - 2807
• Main Authors: Mitchell, James B, Samuni, Amram, Krishna, Murali C, DeGraff, William G, Ahn, Min S, Samuni, Uri, Russo, Angelo
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 20.03.1990
• Subjects: Analytical, structural and metabolic biochemistry; ANIMALS; Biological and medical sciences; BIOLOGICAL FUNCTIONS; CELL CULTURES; Cells, Cultured; Chemical Phenomena; CHEMICAL REACTIONS; Chemistry; Cricetinae; Cytochrome c Group - metabolism; CYTOCHROMES; DNA; DNA - metabolism; ELECTRON SPIN RESONANCE; Electron Spin Resonance Spectroscopy; ENZYMES; Enzymes and enzyme inhibitors; Ferrous Compounds - metabolism; FUNCTIONS; Fundamental and applied biological sciences. Psychology; HAMSTERS; HYDROGEN COMPOUNDS; HYDROGEN PEROXIDE; MAGNETIC RESONANCE; mammalian cells; MAMMALS; Nitrogen Oxides - metabolism; nitroxides; NUCLEIC ACIDS; ORGANIC COMPOUNDS; Oxazoles; Oxidation-Reduction; OXIDOREDUCTASES; OXYGEN COMPOUNDS; PEROXIDES; PIGMENTS; PROTEINS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; REDOX REACTIONS; RESONANCE; RODENTS; SUPEROXIDE DISMUTASE; Superoxide Dismutase - genetics; TOXICITY; VERTEBRATES 560300 > Chemicals Metabolism & Toxicology; Cell culture; Enzyme; EPR spectrometry; Electron transfer; Superoxide dismutase; Antioxidant; Biological activity; Chromatography; Mechanism of action; Chemical synthesis; Protection; Mass spectrometry; Ultraviolet visible spectrometry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00463a024

Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H2O2, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.