FUNCTIONAL STUDIES OF ALTERED HUMAN HEMOGLOBIN

改变的人类血红蛋白的功能研究

• 批准号: 3336051
• 负责人: RICHARD T JONES
• 金额: $ 17.1万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336051
• 关键词: blood /plasma substitute; crosslink; gene mutation; hemoprotein structure; high performance liquid chromatography; human tissue; ion transport; oxygen transport; oxyhemoglobin; peptide chemical synthesis; protein sequence; protein structure function

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.

长期目标是研究人体的功能特性， 血红蛋白已通过突变、化学修饰或 这两个目的都是为了进一步了解 与血红蛋白结合和运输氧有关。 的 结果将用于两个目的。 首先，将努力 将功能特性与结构改变相关联， 更好地了解特定氨基酸残基的贡献 血红蛋白和分子三级和四级的变化 它的氧气运输结构。 第二，功能特性 化学修饰的血红蛋白将被测量和分析， 尝试鉴定和设计可能有用的交联试剂 以血红蛋白为基础的全血输血替代品。 具体目标包括：（1）化学性质 将测量交联的正常血红蛋白和突变血红蛋白， 为了确定导致氧的结构变化， 结合性质在生理学上有用的范围内， 修饰的血红蛋白在溶液中是游离的。 (2)功能异常 血红蛋白将被详细检查，以确定，精确到 可能的，与氧气的整体反应的哪些部分已经被 被突变改变了 (3)以前未研究过的和所有新的 可以获得的异常血红蛋白将被筛查其 氧结合的一般参数，以确定是否 改变的残基影响正常的氧结合。 (4)尝试将 使氧平衡反应的变化与 蛋白质结构，以便更好地了解正常反应 机制及结构与功能的关系。 所用的主要方法是测量氧平衡 反应在其整个范围内的自动记录方法下， pH、离子和温度的各种受控条件。