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.

血红蛋白的自发性自氧化是免疫治疗中的一个重要问题。 化学修饰的血红蛋白作为氧载体的用途。 的 高铁血红蛋白的形成不仅损害氧的运输， 也产生活性氧物质。 汽车机械 尽管交联血红蛋白的氧化不同于化学氧化， 氧化，都遵循共同的途径，其中高铁血红蛋白形成 首先，随后通过形成半色素沉淀。 我们有 他认为，有一个负相关的关系， 这些血红蛋白的自氧化和氧亲和力和稳定性 在溶液中。 存在过量的化学诱导氧化 过氧化氢（1血红素：10 H2 O2）对光谱有显著影响 未修饰血红蛋白的变化指示早期沉淀（10 分钟）。 交联血红蛋白的沉淀发生得晚得多 （>120分钟）。 然而，氧化的四聚体的更大稳定性 用β-β交联的血红蛋白实现溶液中， 而不是在α-α亚基内交联的那些。 我们有 最近扩大了这项工作，通过检查阴离子诱导氧化 使用快速扫描分光光度计， 博士麦克唐纳实验室（莱特曼陆军研究所）。 到目前为止收集的数据已提交，部分，在第四届国际。 血液代用品大会，1991年8月，正在为 出版物