SYNTHESIS AND CHARACTERIZATION OF PDI MIMICS

PDI 模拟物的合成和表征

• 批准号: 6416593
• 负责人: ROBERT J HONDAL
• 金额: $ 1.96万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6416593
• 关键词: analog; catalyst; disulfide bond; enzyme structure; enzyme substrate complex; protein disulfide isomerase; protein engineering; protein structure function

A long sought-after goal of bioorganic chemists is a fundamental understanding of the chemical and structural bases of enzymatic catalysis. A final goal of such insight would be the ability to construct de novo catalysts that could effectively catalyze the desired reactions. This proposal is aimed at constructing small molecule mimics of protein disulfide isomerase (PDI), an enzyme responsible for catalyzing the formation of disulfide bonds in vivo. The design of the mimics is such that they will be able to form a mimic-substrate complex through transient Schiff base formation, and thus better catalysts because the effective concentration of the mimic will be enhanced in the complex. The designed mimics should provide an excellent system for understanding the nature of the actual PDI-substrate complex. If successful, this methodology could be applied to a wide variety of biological reactions and would have potential medical and biotechnological applications.

生物有机化学家长期以来追求的目标是对酶催化的化学和结构基础有基本的了解。 这种见解的最终目标是能够构建能够有效催化所需反应的从头催化剂。 该提案旨在构建蛋白质二硫键异构酶（PDI）的小分子模拟物，PDI是一种负责催化体内二硫键形成的酶。 模拟物的设计使得它们能够通过瞬时席夫碱形成形成模拟物-底物复合物，从而成为更好的催化剂，因为复合物中模拟物的有效浓度将得到提高。 设计的模拟物应该提供一个优秀的系统来理解实际 PDI-底物复合物的性质。 如果成功，这种方法可以应用于多种生物反应，并将具有潜在的医学和生物技术应用。