SYNTHESIS AND BIOCHEMICAL ASSAY OF LEUPEPTIN ANALOGS

亮肽素类似物的合成和生化测定

• 批准号: 3438591
• 负责人: ROSE M MCCONNELL
• 金额: $ 6.04万
• 依托单位: UNIVERSITY OF ARKANSAS AT PINE BLUFF
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3438591
• 关键词: chemical structure function; disease /disorder; enzyme structure; enzyme substrate analog; peptide chemical synthesis; physiology; protease inhibitor; protein engineering; synthetic enzyme; synthetic peptide

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.

蛋白水解酶具有多种生理功能，包括 广义蛋白质消化到特定调节过程 例如酶原的激活、血液凝固、裂解 血栓的形成和血压调节的释放 来自前体蛋白的肽。 具体的酶抑制剂是 通常用作生物分析中的生化工具 功能。 然而，许多蛋白水解酶的确切作用 这种生理过程很难确定 由于目前缺乏特异性酶抑制剂。 胰蛋白酶样丝氨酸肽抑制剂的合成 硫醇蛋白酶，基于天然结构 提出了蛋白酶抑制剂亮肽素。 我们将评估 使用适当的合成类似物的生物效应 酯酶和蛋白酶测定。 这将允许快速 确定合成的抑制剂的有效性， 以及抑制剂结构变化的价值。 在 努力获取信息，从而增强 抑制剂结构活性的选择性和效力 将绘制合成的结构-选择性相关性 抑制剂。 该项目旨在作为一项研究工作，它将允许 本科生有机合成、器乐训练 技术、生化分析和数据统计处理 除了通常不提供的其他研究培训外 在他们的教育的这个阶段，通过加强 这所本科院校的研究环境。