REDOX REACTIVITY OF HEMOGLOBINS--SEARCH FOR A SAFER BLOOD SUBSTITUTE

许多生化反应产生氧自由基， 承认参与发展或促进一些 病理条件。因为它有能力产生或相互作用 与氧自由基，无细胞血红蛋白可被视为有毒的 实质内容。 血红蛋白的自发自氧化是一个重要的问题 使用化学修饰的血红蛋白作为携氧血液 替身 许多修饰和未修饰的人和 动物血红蛋白的超氧化物和过氧化物已被广泛 研究了 这是我们不断寻找动物或突变体的一部分 表现出有利的氧化还原反应的血红蛋白， 希望能使人们更好地了解血红素之间的关系 口袋化学和血红蛋白产生或相互作用的能力， 氧自由基 我们已经获得了候选无细胞 血红蛋白血液替代品，显示其氧化率， 活性氧物质及其细胞色素P450样的产生 活性函数不是由它们的氧亲和力决定的，因此， 氧化和携氧功能可独立选择 参数 在这方面，血红蛋白的潜在氧化毒性 很可能是由其血红素口袋的立体化学决定的。 结果 迄今为止，这项工作已经出版，也 在国家和国际会议上发言。

Many biochemical reactions generate oxygen free radicals that are now recognized to participate in the development or promotion of a number of pathological conditions. Because of its ability to generate or interact with oxygen free radicals, cell-free hemoglobin may be regarded as a toxic substance. Spontaneous autoxidation of hemoglobin is an important concern in the use of chemically modified hemoglobin as an oxygen-carrying blood substitute. Oxidation of a number of modified and unmodified human and animal hemoglobins by superoxide and peroxide have been extensively studied. This is part of our continuous search for animal or mutant hemoglobins that exhibit favorable oxidation- reduction reactions, which we hope will enable a better understanding of the relationship between heme pocket chemistry and the ability of hemoglobin to generate or interact with oxygen free radicals. We have obtained data on candidate cell-free hemoglobin blood substitutes that show that their rates of oxidation, their generation of activated oxygen species and their cytochrome p450-like activity functions are not determined by their oxygen affinities, so that oxidative and oxygen carrying functions are independently selectable parameters. In this regard, the potential oxidative toxicity of hemoglobin may well be determined by the stereochemistry of its heme pocket. Results transpired so far from this work have been published and were also presented at national and international meetings.