DEVELOPMENT AND STUDY OF ENZYME FUNCTIONAL MIMICS

这项研究计划的长期目标是发展高度的- 选择性合成催化剂，像酶一样，能够 识别并选择性地修饰它们的底物。这一点的催化剂 分拣将促进重要的商业生产的高效 治疗学。在追求这一目标的过程中，我们希望做出贡献 超分子催化设计原理。我们将使用组合式 化学制备催化剂库，热成像动力学分析 从这些库和热力学中选择有效的催化剂 结合试验研究底物结合之间的一般关系 和催化作用。 根据这一目标，该提案的具体目标是：1) 开发和定义一种通用方法，该方法基于动力学分析， 允许从大量的催化剂中选择有效的催化剂 裂池组合法制备聚合物结合化合物 合成，2)使用动力学和热力学文库分析 开发和表征具有改性能力的催化剂 具有序列选择性的多肽，3)开发和表征 多功能催化剂，识别过渡态和 促进对映选择性化学反应。

The long-term goal of this research program is to develop highly- selective synthetic catalysts that, like enzymes, have the ability to recognize and selectively modify their substrates. Catalysts of this sort will facilitate the efficient commercial production of important therapeutics. In pursuing this goal, we hope to make contributions to design principles in supramolecular catalysis. We will use combinatorial chemistry to prepare catalyst libraries, thermographic kinetic analysis to select effective catalysts from these libraries and thermodynamic binding assays to study general relationships between substrate binding and catalysis. In accord with this goal, the specific aims of the proposal are: 1) to develop and define a general method that, based on kinetic analysis, allows selection of effective catalysts from large collections of polymer-bound compounds prepared through split-pool combinatorial synthesis, 2) to use kinetic and thermodynamic library analysis to develop and characterize catalysts that have the ability to modify peptides with sequence selectivity, 3) to develop and characterize multi-functional catalysts that recognize transition states and facilitate enantioselective chemical reaction.