FUNCTIONAL STUDIES OF ALTERED HUMAN HEMOGLOBIN

长期目标是研究人类的功能特性 通过突变、化学修饰或其他方式改变的血红蛋白 两者都是为了进一步了解分子机制 通过血红蛋白参与氧的结合和运输。这个 结果将用于两个目的。首先，我们将尝试 将功能特性与结构变化相关联，以便 更好地了解特定氨基酸残基在体内的作用 血红蛋白与分子三、四元组的变化 结构对其氧气运输的影响。第二，函数的性质 化学修饰的血红蛋白将在一个 尝试识别和设计可能有用的交联剂 生产以血红蛋白为基础的全血输注替代品。 具体目标包括：(1)化学上的功能性质 将测量和关联连接的正常和突变的血红蛋白 为了确定导致氧的结构修饰 属性时，处于生理有用范围内的绑定属性 修饰后的血红蛋白在溶液中是游离的。(2)功能异常 将对血红蛋白进行详细检查，以确定 可能，与氧的整个反应的哪些部分已经 被突变改变了。(3)以前没有研究过的，都是新的 将对可获得的异常血红蛋白进行筛查 氧结合的一般参数，以识别是否 改变的残基影响正常的氧结合。(4)尝试将 将氧平衡反应的变化与改变联系起来 蛋白质结构，以便更好地了解正常反应 该蛋白的结构与功能的关系及其作用机制。 使用的主要方法将是测量氧平衡。 全量程反应的自动记录方法 各种pH、离子和温度的控制条件。

The long-term objective is to study the functional properties of human hemoglobins that have been altered by mutation, chemical modification, or both in order to gain further insight into the molecular mechanisms involved in the binding and transport of oxygen by hemoglobin. The results will be used for two purposes. First, attempts will be made to correlate functional properties with structural alterations in order to better understand the contributions of specific amino acid residues in hemoglobin and changes in the molecule's tertiary and quaternary structures to its oxygen transport. Second, functional properties of chemically modified hemoglobins will be measured and analyzed in an attempt to identify and design cross-linking reagents that may be useful in producing hemoglobin-based substitutes for whole blood transfusion. The specific aims include: (1) The functional properties of chemically cross-linked normal and mutant hemoglobins will be measured and correlated in order to identify structural modifications that result in oxygen binding properties that are in a physiologically useful range when the modified hemoglobin is free in solution. (2) Functionally abnormal hemoglobins will be examined in detail to determine, as precisely as possible, which parts of the overall reaction with oxygen have been altered by the mutational change. (3) Previously unstudied and all new abnormal hemoglobins that can be obtained will be screened for their general parameters of oxygen binding in order to identify whether or not the altered residue influences normal oxygen binding. (4) Attempts will be made to correlate changes in oxygen equilibrium reaction with altered protein structure in order to better understand the normal reaction mechanism and the relation of the structure and function of this protein. The principal methods used will be the measurement of oxygen equilibrium reaction over its full range by the automatic recording method under various controlled conditions of pH, ions, and temperature.