AUTOOXIDATION AND STABILITY OF CROSSLINKED HEMOGLOBINS

交联血红蛋白的自动氧化和稳定性

• 批准号: 3804884
• 负责人: A I ALAYASH
• 金额: --
• 依托单位: CENTER BIOLOGICS EVALUATION RESEARCH HEMATOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3804884
• 关键词: autooxidation; blood /plasma substitute; crosslink; hemoglobin; human tissue; hydrogen peroxide; methemoglobin; oxidation; oxygen transport; peptide analog; protein structure function; spectrometry

Spontaneous autoxidation of hemoglobin is an important concern in the use of chemically modified hemoglobin as an oxygen carrier. The formation of methemoglobin not only compromises the oxygen transport but also gives rise to reactive oxygen species. The mechanism of auto oxidation of crosslinked hemoglobins though is different from chemical oxidation, both follow common pathway in which methemoglobin is formed first followed by precipitation via hemichrome formation. We have established that there is an inverse relationship between the rate of autoxidation and the oxygen affinity and stability of these hemoglobins in solution. Chemically induced oxidation in presence of excess hydrogen peroxide (1 heme:10 H2O2) had a striking effect on the spectral change of unmodified hemoglobin indicative of an early precipitation (10 minutes). Precipitation of crosslinked hemoglobins occurs much later (>120 minutes). However, greater stabilization of the oxidized tetramer in solution was achieved with the Beta-Beta crosslinked hemoglobins as opposed to those crosslinked within the alpha-alpha subunits. We have recently expanded on this work by examining the anion-induced oxidation of crosslinked hemoglobins using a fast scanning spectrophotometer in Dr. V. Macdonald's laboratory (at Letterman Army Institute of Research). Data collected so far has been presented, in part, at the IVth Int. Congress on Blood Substitutes, August, 1991 and is being compiled for publication.

自氧化的血红蛋白是一个重要的关注在 使用化学修饰的血红蛋白作为氧气载体。这个 高铁血红蛋白的形成不仅影响氧气的运输，而且 也会产生活性氧物种。自动驾驶的机理 交联血红蛋白的氧化不同于化学氧化 氧化，两者都遵循高铁血红蛋白形成的共同途径 首先是通过半铬层形成的降水。我们有 确定了在这一比率之间存在反向关系 自氧化作用与这些血红蛋白的氧亲和力和稳定性 在溶液中。在过量存在时化学诱导的氧化 过氧化氢(1：10)对光谱有显著影响 未修饰的血红蛋白的变化表明早期沉淀(10 分钟)。交联型血红蛋白沉淀发生的时间要晚得多。 (&gt；120分钟)。然而，氧化四聚体的稳定性更好 以贝塔-贝塔交联型血红蛋白为 而不是阿尔法-阿尔法亚基中的那些交联体。我们有 最近通过研究阴离子诱导的氧化来扩展这项工作 使用快速扫描分光光度计测交联型血红蛋白 麦克唐纳博士的实验室(莱特曼陆军研究所)。 到目前为止收集的数据已部分在第四届国际会议上公布。 血液代用品大会，1991年8月，正在为 出版。