HETEROGENEOUS NUCLEATION AND SICKLE CELL DISEASE

异质成核和镰状细胞病

• 批准号: 2839069
• 负责人: FRANK A FERRONE
• 金额: $ 18.52万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-20 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839069
• 关键词: animal tissue; biophysics; chemical kinetics; erythrocytes; hemoglobin F; hemoglobin Ss; lasers; mutant; nucleolus; oxygen transport; photolysis; polymerization; polymers; sickle cell anemia; video microscopy

DESCRIPTION: Adapted from the investigator s abstract: Sickle cell disease arises from the polymerization of sickle hemoglobin by a double nucleation mechanism involving homogenous nucleation in solution and heterogeneous nucleation into sickle hemoglobin polymer surfaces. While the conceptual features of that mechanism have been validated, its predictive power is limited by the lack of a structural foundation and a flawed description of heterogeneous nucleation in the presence of non-polymerizing molecules. The experimental core of this proposal is to assemble a data base of solubility (csat), homogeneous and heterogeneous nucleation rates and elongation rates, for sickle hemoglobin assembly as a function of solution conditions (T, pH, non-ideality) and for various amino acid substitutions. Sickle hemoglobin mutants with additional amino mutations will primarily be provided by Dr. James Manning of Rockefeller University, and the hemoglobin of the SAD mouse will be provided by Dr. Frank Costantini of Columbia University. These data will be used to test and refine a new structural model for heterogeneous nucleation which are proposed herein. The data will also allow the description of heterogeneous nucleation to be extended to describe gelation in the presence of oxygen, fetal Hb, or other non-polymerizing species. This work will ultimately provide an energetic map of the interactions which create the rigid, vasoocclusive gel.

描述：改编自调查员的摘要：镰状细胞病 由镰状血红蛋白通过双成核的聚合产生 涉及溶液和异质中均匀成核的机制 成核成镰状血红蛋白聚合物表面。 而概念 该机制的特征已得到验证，其预测能力是 受结构基础缺乏的限制和有缺陷的描述 在存在非聚合分子的情况下，异质成核。 该提案的实验核心是组装 溶解度（CSAT），均质和异质成核率以及 伸长率，镰状血红蛋白组装作为溶液的函数 条件（T，pH，非理想性）和各种氨基酸取代。 具有其他氨基突变的镰状血红蛋白突变体将主要是 由洛克菲勒大学的詹姆斯·曼宁博士和血红蛋白提供 哥伦比亚的弗兰克·科斯坦蒂尼（Frank Costantini）博士将提供悲伤的鼠标 大学。 这些数据将用于测试和完善新的结构模型 本文提出的异质成核。 数据也将 允许对异质成核的描述进行扩展以描述 在氧，胎儿HB或其他非聚合的存在下凝胶化 物种。 这项工作最终将提供一个充满活力的地图 产生刚性的血管含量凝胶的相互作用。