SYNTHESIS AND BIOCHEMICAL ASSAY OF LEUPEPTIN ANALOGS

蛋白水解酶有许多生理功能，包括 对特定调控过程的广义蛋白质消化 如酵母菌的激活，凝血，裂解 祛除血栓，调节血压的释放 来自前体蛋白的多肽。特定的酶抑制剂有 通常用作生物分析中的生化工具 功能。然而，许多蛋白水解酶在 这种生理过程一直很难确定 因为目前缺乏特定的酶抑制剂。 类胰酶丝氨酸和丝氨酸多肽抑制剂的合成 硫醇蛋白酶，这是基于天然的结构 提出了蛋白水解酶抑制剂亮氨酸的概念。我们将评估 适当使用合成类似物的生物学效应 酯酶和蛋白水解酶测定。这将允许快速 合成的缓蚀剂的有效性的测定， 以及在抑制剂结构中所做的改变的价值。在……里面 为获取信息而做出的努力 缓蚀剂构效关系的选择性和有效性 将为合成的化合物绘制结构-选择性关联 抑制剂。 这个项目是作为一项研究工作设计的，它将使 本科生有机合成、仪器类专业培养 技术、生化分析和数据的统计处理 除了通常不提供的其他研究培训 在他们教育的这个阶段，通过加强 这所本科院校的研究环境。

Proteolytic enzymes have many physiological functions, ranging from generalized protein digestion to specifically regulated processes such as the activation of zymogens, blood coagulation, the lysis of blood clots, and the release of blood pressure regulating peptides from precursor proteins. Specific enzyme inhibitors are normally used as biochemical tools in the analysis of biological functions. However, the exact role of many proteolytic enzymes in such physiological processes has been difficult to determine because of a current lack of specific enzyme inhibitors. The synthesis of peptide inhibitors of trypsin-like serine and thiol proteinases, which are based on the structure of the natural proteinase inhibitor, leupeptin, is proposed. We will evaluate the biological effects of the synthetic analogs using appropriate esterase and proteinase assays. This will allow for a rapid determination of the effectiveness of the inhibitors synthesized, and the value of the changes made in the inhibitor structure. In an effort to gain information leading to the enhancement of the selectivity and potency of inhibitors structure-activity and structure-selectivity correlations will be drawn for the synthetic inhibitors. This project was designed as a research effort which will allow undergraduate students training in organic synthesis, instrumental techniques, biochemical analysis, and statistical treatment of data in addition to other research training not normally available at this stage in their education, through an enhancement of the research environment at this undergraduate institution.