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.

有了这个奖项，有机和高分子化学计划继续支持得克萨斯大学奥斯汀分校化学系的Eric V. Anslyn博士的工作。 这项工作的目的是制备人工磷酸酯酶能够切割RNA的速度和选择性媲美的天然酶。 该方法涉及系统的结构变化周围的刚性hexasubitated苯核心与连接亲电Zn（+2）和胍阳离子位点。 利用动力学、平衡结合常数的测量、pH滴定和晶体学研究金属离子位点之间以及金属离子与胍之间的协同性。通过制造小的紧密空腔，DNA可以与带正电荷的锌或胍离子形成至少四个和多达六个氢键，从而开发出能够切割DNA的人工酶。 这些新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有一个优秀的教师和研究导师的记录，并帮助了一些女研究生去获得博士学位。