Highly Preorganized Artificial Phosphoesterases

凭借这一奖项，有机和高分子化学项目继续支持德克萨斯大学奥斯汀分校化学系埃里克·V·安斯林博士的工作。这项工作旨在制备能够以与天然酶相媲美的速率和选择性来裂解RNA的人工磷酸酯酶。该方法涉及到刚性的六取代苯核周围的系统结构变化，以及附着的亲电锌(2)和胍阳离子中心。将通过动力学、平衡结合常数的测量、pH滴定和结晶学来研究金属离子中心之间以及金属离子和胍离子之间的协作性。可以通过制造小而紧密的空腔来开发能够切割DNA的人造酶，在空腔中DNA可以与带正电的锌离子或胍离子形成至少四个甚至多达六个氢键。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。如果能够开发出有效的催化剂，它们将在基因治疗中发挥作用。PI作为一名优秀的教师和研究导师的记录，并帮助了一些女研究生继续获得博士学位。

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.