SYNTHESIS AND CHARACTERIZATION OF PDI MIMICS

生物有机化学家长期追求的目标是对酶催化的化学和结构基础有一个基本的了解。这种洞察力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。这项建议旨在构建蛋白质二硫键异构酶(PDI)的小分子模拟物，PDI是一种在体内负责催化二硫键形成的酶。模拟物的设计是这样的，它们将能够通过瞬时Schiff碱的形成形成模拟底物络合物，从而形成更好的催化剂，因为模拟物在络合物中的有效浓度将被提高。所设计的模拟电路应该为理解实际的PDI-底物复合体的性质提供一个很好的系统。如果成功，这种方法可以应用于各种各样的生物反应，并将具有潜在的医疗和生物技术应用。

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.