Teaching and Research at the Interface of Chemistry and Biology

这项研究的重点是研究哺乳动物受精过程中发生的蛋白质-蛋白质相互作用。当精子蛋白受精素与卵子质膜结合时发生的配体相互作用将被解剖，推测是在受体上。具体地说，将合成谷氨酸-半胱氨酸-天冬氨酸去整合素环和受精素的表皮生长因子样模块的多肽模拟物，并测试它们抑制精子-卵子融合的能力。突变的多肽将被测试以识别对抑制重要的残基，良好的抑制剂将被开发成亲和标记。这些标记将被用来识别卵质膜上的受体(S)。此外，受精素的结构域将使用重组DNA方法表达，并将测试它们抑制精子-卵子融合的能力。这些结构域将被用作亲和配体来分离它们的受体，并将通过核磁共振波谱获得有关结构域的信息。定点突变实验将确定对结合、融合和信号转导重要的残基。教育计划将侧重于本科课程的发展，以及化学和生物交界处的博士培养计划的发展。通过这个职业奖项，合成有机项目支持纽约州立大学石溪分校化学系的Nicole S.Sampson博士的研究和教育活动。桑普森教授将把她的研究重点放在研究哺乳动物受精过程中的蛋白质相互作用上。这项工作的好处在于开发更好、更具体的避孕药，并发现不孕不育的遗传原因，然后可以绕过这些原因。该教育计划将侧重于开发一门关于生物化学趋势的本科课程，并为化学和生物交界处的博士培养计划制定教学计划。

The focus of this research is to investigate protein-protein interactions that occur during mammalian fertilization. The ligand interactions that occur upon binding of the sperm protein fertilin to the egg plasma membrane, presumably at a receptor, will be dissected. Specifically, peptido-mimetics of the glutamate- cysteine-aspartate disintegrin loop and the epidermal growth factor-like module of fertilin will be synthesized and tested for their ability to inhibit sperm-egg fusion. Mutant peptides will be tested to identify residues important for inhibition and good inhibitors will be developed into affinity labels. These labels will be used to identify the receptor(s) in the egg-plasma membrane. Also, the domains of fertilin will be expressed using recombinant DNA methodology and will be tested for their ability to inhibit sperm-egg fusion. The domains will be used as affinity ligands for the isolation of their receptors and information about the structure of the domains will be obtained with NMR spectroscopy. Site-directed mutagenesis experiments will identify residues important for binding, fusion and signaling. The educational plan will focus on undergraduate course development and also on the development of a Ph.D. training program at the interface of chemistry and biology. With this CAREER award, the Synthetic Organic Program supports the research and educational activities of Dr. Nicole S. Sampson of the Department of Chemistry at SUNY, Stony Brook. Professor Sampson will focus her research efforts on investigating the protein-protein interactions that occur during mammalian fertilization. The benefit of the work lies in the development of better, more specific contraceptives and in discovering the genetic reasons for infertility which could then be circumvented. The educational plan will focus on the development of an undergraduate course on trends in biological chemistry and the the construction of a teaching plan for a Ph.D. training program at the interface of chemistry and biology.