Highly Preorganized Artificial Phosphoesterases

高度预组织的人工磷酸酯酶

• 批准号: 9988615
• 负责人: Eric Anslyn
• 金额: $ 34.1万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9988615&HistoricalAwards=false
• 关键词: Highly; Preorganized; Artificial; Phosphoesterases

With this award the Organic and Macromolecular Chemistry Program continues its support for the work of Dr. Eric V. Anslyn in the Department of Chemistry at the University of Texas at Austin. The work aims to prepare artificial phosphoesterase enzymes capable of cleaving RNA with rates and selectivities rivaling those of the natural enzymes. The approach involves systematic structural variations around a rigid hexasubstituted benzene core with attached electrophilic Zn(+2) and guanidinium cation sites. Cooperativity between metal ion sites and between metal ions and guanidinium will be investigated using kinetics, measurements of equilibrium binding constants, pH titrations, and crystallography.Artificial enzymes which can cleave DNA will be developed by making small tight cavities in which DNA can form at least four and as many as six hydrogen bonds to positively charged zinc or guanidinium ions. The keys to these new catalysts are the large number of potential binding interactions and the rigidity of the cavity walls. If effective catalysts can be developed they would be useful in gene therapy. The PI has a record of being an excellent teacher and research mentor, and has helped a number of female graduate students to go on to get PhDs.

通过这个奖项，有机和大分子化学项目继续支持德克萨斯大学奥斯汀分校化学系Eric V. Anslyn博士的工作。本研究旨在制备具有与天然酶相媲美的速率和选择性的人工磷酸酯酶。该方法涉及围绕刚性六取代苯核的系统结构变化，并附有亲电性Zn（+2）和胍离子位点。金属离子位点之间以及金属离子与胍之间的协同作用将通过动力学、平衡结合常数测量、pH滴定和晶体学进行研究。可以切割DNA的人工酶将通过制造小而紧密的空腔来开发，在这些空腔中，DNA可以与带正电的锌或胍离子形成至少4到6个氢键。这些新型催化剂的关键是大量潜在的结合相互作用和腔壁的刚性。如果能开发出有效的催化剂，它们将在基因治疗中发挥作用。PI是一名优秀的教师和研究导师，并帮助许多女研究生继续获得博士学位。