DEVELOPMENT AND STUDY OF ENZYME FUNCTIONAL MIMICS

酶功能模拟物的开发与研究

• 批准号: 6520031
• 负责人: JAMES Patrick MORKEN
• 金额: $ 15.49万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6520031
• 关键词: catalyst; chemical binding; combinatorial chemistry; drug design /synthesis /production; enzyme mechanism; enzyme substrate complex; peptide library; stereochemistry; synthetic enzyme

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.

这项研究计划的长期目标是高度发展- 选择性的合成催化剂，像酶一样，有能力 识别并选择性地修饰它们的底物。催化剂对此 排序将促进重要的高效商业生产， 治疗学在追求这一目标的过程中，我们希望为以下方面作出贡献： 超分子催化的设计原理我们将使用组合 化学制备催化剂库，热成像动力学分析 从这些库中选择有效的催化剂， 研究底物结合之间一般关系的结合试验 和催化作用。 雅阁这一目标，该提案的具体目标是： 开发和定义一种通用方法，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， 聚合物结合的化合物通过分-池组合制备 合成，2）使用动力学和热力学库分析， 开发和表征具有改性能力的催化剂 具有序列选择性的肽，3）开发和表征 识别过渡态的多功能催化剂， 促进对映选择性化学反应。