CROSSLINKED HEMOGLOBINS

交联血红蛋白

• 批准号: 6110154
• 负责人: ENRICO BUCCI
• 金额: $ 23.77万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110154
• 关键词: alkylating agents; aspirin; chemical structure; chemical substitution; chemical synthesis; crosslink; dicarboxylate; glomerular filtration rate; hemoglobin; high performance liquid chromatography; ion exchange chromatography; kidney circulation; kidney function; laboratory rat; oxygen transport; thermodynamics; thiols

The scope of this project is the chemical development of oxygen carriers, and their screening and testing on kidney function. Specific aims include: 1) exploitment of the versatility of polyaspirin reagents for obtaining oxygen carriers with lower oxygen affinity, higher cooperativity and diminished urine elimination, 2) to search for controllable inter-molecular crosslinks of hemoglobin molecules, 3) to screen biological viability of the oxygen carriers by measuring retention time, urine elimination, acute and chronic renal effects. We will explore the use of di- and tri-aspirins for intramolecular crosslinks which will lower the oxygen affinity and decrease urine elimination; long carbon chains diaspirins, bis-maleimido and bis-alkylating agents will be used for producing controllable inter-molecular crosslinks. For obtaining hemoglobin octamers we will synthesize crosslinkers where two bifunctional reagents are joined by a branched carbon chain. Functional tests will characterize the thermodynamics of the intermediates of oxygenation in the oxygen carriers as compared to that of normal hemoglobin. This will give useful information for the engineering of oxygen carriers.

该项目的范围是氧载体的化学开发， 以及他们的肾功能筛查和检测。 具体目标 包括：1）利用聚阿司匹林试剂的多功能性， 获得具有较低的氧亲和力、较高的 协同性和减少尿液排泄，2）寻找 血红蛋白分子的可控分子间交联，3） 通过测量保留来筛选氧载体的生物活性 时间、尿液消除、急性和慢性肾脏影响。 我们将 探索使用二-和三-阿司匹林进行分子内交联 这将降低氧亲和力并减少尿液排泄;长 碳链二阿司匹林、双马来酰亚胺和双烷基化剂将 用于产生可控的分子间交联。 为 获得血红蛋白八聚体，我们将合成交联剂，其中两个 双官能试剂通过支链碳链连接。 功能 测试将表征中间体的热力学， 氧载体中的氧合，与正常 血红蛋白。 这将为工程设计提供有用的信息。 氧载体