BIOLOGICALLY-ACTIVE METAL-INDEPENDENT SUPEROXIDE-DISMUTASE MIMICS
BIOLOGICALLY-ACTIVE METAL-INDEPENDENT SUPEROXIDE-DISMUTASE MIMICS
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DOI：
10.1021/bi00463a024
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发表时间：
1990-03-20
期刊：
影响因子：
2.9
通讯作者：
RUSSO, A
中科院分区：
文献类型：
--
作者：
MITCHELL, JB;SAMUNI, A;RUSSO, A
超氧化物歧化酶（SOD）是一种解毒超氧化物（O2.-）的酶，一种潜在的有毒氧衍生物通过直接应用增加SOD的细胞内浓度的尝试是复杂的，因为SOD是相对大的分子，不容易穿过细胞膜。我们已经鉴定了一组稳定的氮氧自由基，其具有SOD样活性，具有低分子量、膜渗透性和不依赖于金属的优点，并且在pH 7.0下具有与O2的反应速率常数。范围为1.1 × 1.5 ~ 1.5 × 1.5。103至1.3 ×106 M-1 S-1这些SOD模拟物保护哺乳动物细胞免受次黄嘌呤/黄嘌呤氧化酶和H2 O2诱导的损伤，尽管它们没有表现出过氧化氢酶样活性。此外，氮氧化物SOD模拟物快速氧化DNA-Fe II，因此可以中断芬顿反应并防止形成有害的OH自由基和/或更高氧化态的金属离子。无论是通过SOD样活性和/或从氧化还原活性金属离子截取电子，它们都保护细胞免受氧化应激，并可用于基础和应用生物学研究。
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 .times. 103 to 1.3 .times. 106 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.