NOVEL ORGANIC REAGENTS FOR BIOMEDICAL APPLICATIONS

用于生物医学应用的新型有机试剂

• 批准号: 6258823
• 负责人: Ramachandra S Hosmane
• 金额: $ 0.02万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6258823
• 关键词: Mammalia; biological products; biomedical resource; biotechnology; drug screening /evaluation; proteins; technology /technique development

Artificial Blood for Emergency Transfusions: Guided by computer-assisted molecular modeling, we design and synthesize novel polyfunctional organic reagents to cross-link cell-free hemoglobin. These modified hemoglobins will potentially serve as substitutes for whole blood for emergency transfusions, and would require no typing or cross-matching, be free of bacteria or viruses, and storable as a dry powder for indefinite periods of time. The cross-linking is anticipated to prevent the otherwise rapid renal elimination of cell-free hemoglobins, while also decreasing the latters oxygen affinity, so as to afford adequate oxygen and carbon dioxide transport from lungs to tissues and vice versa. To accomplish the above goal, we need an access to high mass analysis in the range of 32,000-33,000 by MALDI-MS. Each of the four hemoglobin subunits, ?1, ?1, ?2, ?2, weighs approximately 16,000 Daltons. When cross-linked, they form a dimer of ?32,000 Daltons. Therefore, MALDI-MS would enable us to conveniently a) analyze the cross-linking patterns, and b) in conjunction with tryptic digestion, map regions where cross-linking has occurred.

紧急输血的人造血：由 计算机辅助分子建模，我们设计和合成新颖 多功能有机试剂，可与无细胞的血红蛋白交联。 这些改良的血红蛋白将有可能用作替代品 全血以用于紧急输血，不需要打字或 交叉匹配，不含细菌或病毒，并且可以作为干燥 粉末无限期。 交联是 预计会防止原本快速的肾脏消除 无细胞的血红蛋白，同时还降低了后者的氧气 亲和力，以便提供足够的氧气和二氧化碳运输 从肺到组织，反之亦然。 为了实现上述目标， 我们需要访问32,000-33,000的高质量分析 由Maldi-MS。 四个血红蛋白亚基，？1，？1，？2，？2， 重约16,000个达尔顿。 交联后，它们会形成一个 32,000 daltons的二聚体。 因此，Maldi-MS将使我们能够 方便地a）分析交联模式，b） 与胰蛋白酶消化的结合，地图区域的交联区域 发生了。