NOVEL ORGANIC REAGENTS FOR BIOMEDICAL APPLICATIONS

紧急输血用人工血： 计算机辅助分子模拟，我们设计和合成新的 多官能有机试剂来交联无细胞血红蛋白。 这些修饰的血红蛋白将有可能作为 全血用于紧急输血，不需要打字或 交叉匹配，不含细菌或病毒，可作为干品储存 无限期使用粉末。 交联是 预计可防止肾脏快速消除 无细胞血红蛋白，同时也减少后者的氧气 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。 为实现上述目标， 我们需要在32，000 - 33，000范围内进行高质量分析 通过MALDI-MS。每四个血红蛋白亚基，？1、？1、？2、？2, 重约一万六千道尔顿 当交联时，它们形成 二聚体？三万两千道尔顿。 因此，MALDI-MS将使我们能够 方便地a）分析交联模式，和B）在 结合胰蛋白酶消化，绘制交联区域， 已经发生了。

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.