Affinity Interactions in Capillary Separations

密歇根大学安娜堡分校的Robert T. Kennedy教授在化学系分析和表面化学项目的支持下，开发毛细管电泳方法来检测和量化蛋白质之间的相互作用，并测量酶的活性。将被研究的模型结合系统包括G蛋白、G蛋白信号调节因子（RGS蛋白）和结合磷酸化蛋白的sh2结构域蛋白。酶系统包括g蛋白水解GTP和腺苷基环化酶催化形成环amp。检测受体激动剂和这些反应的蛋白质调节剂的作用将被证明。生命过程依赖于蛋白质之间的亲和相互作用来调节细胞中化学反应发生的时间和地点。理解生命化学的进步依赖于定量亲和相互作用的方法，比如这里所开发的方法。这些方法也将适用于筛选天然产物混合物和药物文库，以高通量发现改变这些相互作用的药物。这项工作将包括对具有仪器开发和生物化学经验的学生进行高水平培训，以支持科学基础设施。

Professor Robert T. Kennedy of the University of Michigan Ann Arbor is supported by the Analytical and Surface Chemistry Program in the Division of Chemistry to develop capillary electrophoresis methods to detect and quantify protein-protein interactions and to measure enzymatic activity. The model binding systems that will be investigated include G proteins, regulators of G protein signaling (RGS proteins), and SH2-domain proteins that bind phosphoproteins. The enzymatic systems include G-protein hydrolysis of GTP and adenylyl cylcase catalyzed formation of cyclic-AMP. Detection of the effects of receptor agonists and protein regulators of these reactions will be demonstrated. Life processes rely on affinity interactions between proteins to regulate when and where chemical reactions occur in cells. Advancements in understanding the chemistry of life rely on methods, such as those developed here, for quantifying affinity interactions. The methods will also be adapted to screening of natural product mixtures and libraries of pharmaceuticals for high-throughput discovery of drugs that alter these interactions. The work will involve high-level training of students with experience in both instrument development and biochemistry to support the scientific infrastructure.