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

佐治亚大学的瑞安·希利教授得到化学系化学催化计划的支持，开发了一个以DNA为编码元件的小分子催化剂发现平台。从用于医药的精细化学品到用作塑料的聚合物等大宗化学品，键形成反应对于构建分子都是必不可少的。高效和选择性地构建这些键需要催化剂。这项研究有望通过快速筛选大量化学物质以获得所需的催化活性，从而极大地加快发现新催化剂的速度。从如此大的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。更高效和更有选择性的催化剂可以生产更多所需产品，同时减少浪费，缩短进入消费市场的时间。这项研究与跨学科的教育和培训活动以及高中、本科生和研究生层面的推广活动相结合。HILI集团致力于本科生研究，本科生对他们实验室的强烈参与和本科生共同撰写的论文证明了这一点。希利教授致力于在UGA重建美国化学学会分会的学生附属机构，以促进化学研究对社会的影响。他还努力增加对Young Dawgs STEM计划的参与，该计划旨在识别当地的高中生，并将他们安置在佐治亚大学的研究实验室，以获得第一手的科学研究知识和经验。该项目概述了以可溶于水介质和无水有机溶剂的两亲性DNA为编码元件的小分子催化剂体外选择平台的开发。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。目前的目标是确定两亲性DNA作为编码元件在各种催化反应中的相容性；开发方法来生成和筛选两亲性DNA编码的化学库，用于在各种溶剂中的催化活性；以及应用该方法来筛选库中单个催化剂的动力学参数。与现有催化剂发现技术相比，拟议研究的优势是：(1)更高的吞吐量，库成员很容易超过100万个库成员；(2)使用少量的库材料；(3)溶液相动力学；(4)能够在一个测序实验中轻松地多个时间点、反应条件和不同的底物；以及(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.