HEMOGLOBIN BASED OXYGEN CARRIERS

研究人和牛血红蛋白以获得 可用于保健输送的氧载体 程序. 必须克服三个主要困难： 血管内滞留时间和高氧亲和力 无细胞条件下的血红蛋白和血管毒性 存在于溶血产物中。 牛血红蛋白尤其 研究其溶血产物。 牛血红蛋白将是 特别是研究其独特的功能特性 即其氧亲和力对阴离子的强敏感性， 对多磷酸盐相对不敏感。 在牛血红蛋白中 在β 1位有一个蛋氨酸，它取代了 人血红蛋白中β 1-β 2位的Val-His二肽。 这可能是负责不同的功能态度， 人和牛血红蛋白。 反应性牛脱氧血红蛋白 使用富马酰二阿司匹林， 在pH 7.4时，P50接近60 mmHg。 有一个分子内 这种化合物的β亚基之间的交联，而 相同的反应在α亚基之间产生交联， 人血红蛋白。 正如已经注意到的人溶血产物， 牛溶血产物抑制由 内皮源性舒张因子在兔主动脉环中的表达。 他们 不抑制β受体。 该项目的具体目标是 1)为了阐明牛血红蛋白的特殊相互作用 与一价和多价阴离子，探讨可能的作用， 在这些现象中的β 1位的蛋氨酸。 2)阐明血红蛋白的结构与功能关系 其四聚体结构已通过分子内 交叉连接。 3)用温和的方法延长血红蛋白的保留时间， 聚合和通过改变它们的流体动力学体积。 4)阐明血管毒性的药理学来源 血红蛋白溶液。

Human and bovine hemoglobins are investigated for obtaining oxygen carriers which could be used in health care delivery procedures. Three main difficulties must be overcome: the short intravascular retention time and the high oxygen affinity of hemaglobin, in cell-free conditions and the vascular toxicity present in hemolysates. Bovine hemoglobin will be especially investigated for its hemolysates. Bovine hemoglobin will be especially investigated for its peculiar functional characteristics namely the strong sensitivity of its oxygen affinity to anions and the relative insensitivity to polyphosphates. In bovine hemoglobin there is a methionine in position beta1, which substitutes for the Val-His dipeptide in position beta1-beta2 in human hemoglobin. This may be responsible for the different functional attitudes of human and bovine hemoglobins. Reacting bovine deoxyhemoglobin with fumaryl diaspirin it is possible to obtain an oxygen carrier with P50 near 60 mmHg at pH 7.4. There is an intramolecular crosslink between the beta subunits of this compound, while the same reaction produces a crosslink between the alpha subunits in human hemoglobin. As already noticed for human hemolysates, bovine hemolysates inhibit the relaxation produced by endothelium derived relaxing factor in rings of rabbit aorta. They do not inhibit the beta receptor. Specific goals of the project are 1) To elucidate the peculiar interaction of bovine hemoglobin with mono and polyvalent anions, exploring the possible role of the methionine at beta1 in these phenomena. 2) To elucidate the structure function relationship in hemoglobins whose tetrameric structure has been stabilized by intramolecular crosslinks. 3) To prolong the retention time of hemoglobins by mild polymerization and by modifying their hydrodynamic volume. 4) To clarify the pharmacological origin of the vascular toxicity of hemoglobin solutions.