High-Throughput Small-Molecule Catalyst Discovery using Amphiphilic DNA-Encoded Libraries

格鲁吉亚大学的Ryan Hili教授得到化学系化学催化项目的支持，开发了一个使用DNA作为编码元件的小分子催化剂发现平台。成键反应对于构建从医药中使用的精细化学品到大宗化学品（如用作塑料的聚合物）的分子至关重要。需要催化剂来有效和选择性地构建这些键。 这项研究预计将大大加快新催化剂的发现，使大型化学品库能够快速筛选所需的催化活性。 从这样的大屏幕上获得的信息可以用来制造更好的催化剂，并增加我们对有助于催化的分子相互作用的理解。 更有效和选择性更高的催化剂可以生产更多的所需产品，同时减少浪费和消费者市场的时间。 这项研究与高中，本科和研究生层面的跨学科教育和培训活动以及外展活动相结合。 Hili集团致力于本科生研究，其实验室的本科生参与以及本科生合著的论文证明了这一点。教授Hili工程重建UGA的美国化学学会章的学生会员，以促进化学研究对社会的影响。他还努力增加参与年轻的道格干程序，这是一个程序，确定当地高中学生，并把他们在格鲁吉亚研究实验室的大学，以获得第一手的知识和经验，在科学研究。 该项目概述了小分子催化剂的体外选择平台的开发，使用两亲性DNA作为编码元件，该DNA可溶于水介质和无水有机溶剂。最终目标是将高通量DNA测序与小分子成键催化剂的发现结合起来。 直接目的是确定在各种催化反应期间作为编码元件的两亲性DNA的相容性;开发用于产生和筛选两亲性DNA编码的化学文库在各种溶剂中的催化活性的方法;以及应用该方法筛选文库内的单个催化剂的动力学参数。与现有的催化剂发现技术相比，所提出的研究的优点是：（1）更高的通量，文库容易超过一百万个文库成员;（2）使用少量的文库材料;（3）溶液相动力学;（4）在一个测序实验中容易地多路复用时间点、反应条件和不同底物的能力;和（5）减少通常伴随高通量筛选工作的材料/溶剂浪费。

Professor Ryan Hili of the University of Georgia is supported by the Chemical Catalysis Program of the Division of Chemistry to develop a discovery platform for small molecule catalysts using DNA as an encoding element. Bond-forming reactions are essential to construct molecules ranging from fine chemicals used in medicine to bulk chemicals such as polymers used as plastics. Catalysts are needed to construct these bonds efficiently and selectively. This research is anticipated to greatly accelerate the discovery of new catalysts by enabling large libraries of chemicals to be screened quickly for desired catalytic activity. The information garnered from such large screens can be used to create better catalysts and to increase our understanding of the molecular interactions that contribute to catalysis. Catalysts that are more efficient and selective produce more of the desired product and, at the same time, reduce waste and time to consumer markets. This research is integrated with interdisciplinary educational and training activities and outreach at the high school, undergraduate, and graduate levels. The Hili Group is dedicated to undergraduate research, as evidenced by strong undergraduate participation in their lab, and by papers co-authored by undergraduates. Professor Hili works to rebuild the Student Affiliates of the American Chemical Society chapter at UGA to promote the impact of chemistry research on society. He also strives to increase participation in the Young Dawgs STEM Program, which is a program that identifies local area high school students and places them in University of Georgia research laboratories to gain first-hand knowledge and experience in scientific research. The project outlines the development of an in vitro selection platform for small molecule catalysts using amphiphilic DNA, which is soluble in aqueous media and anhydrous organic solvents, as an encoding element. The ultimate goal is to couple high-throughput DNA sequencing to the discovery of small-molecule bond-forming catalysts. The immediate aims are to determine the compatibility of amphiphilic DNA as an encoding element during various catalytic reactions; to develop methods to generate and screen an amphiphilic DNA-encoded chemical library for catalytic activity in various solvents; and to apply the method to screen en masse the kinetic parameters of individual catalysts within the library. The advantages of the proposed research over existing catalyst discovery technologies are: (1) higher throughput, with libraries easily exceeding one million library members; (2) the use of small amounts of library material; (3) solution-phase kinetics; (4) the ability to easily multiplex time-points, reaction conditions, and different substrates in one sequencing experiment; and (5) the reduction of material/solvent waste that typically accompanies high-throughput screening efforts.