Development of Sequence-Specific Bioorthogonal Reactions

有了这个奖项，化学部的生命过程化学计划正在资助布法罗的纽约州立大学的Qing Lin博士使用基于噬菌体的方法来进化含炔的肽，用于序列特异性钯介导的与芳基碘试剂的交叉偶联反应，以及含半胱氨酸的肽与含腈的小分子探针的缩合反应。通过利用生物学技术，如噬菌体展示，可以询问多达6000亿个含有独特化学官能团的肽底物的反应性。 将研究氨基酸序列对上述肽的反应性的影响。 本论文将利用动力学和核磁共振（NMR）方法探讨这两个生物正交反应的结构基础和机理。 这项拟议中的研究旨在为重要的生物学问题的研究带来新的化学工具。该项目解决了在生命系统内应用的有机反应发展中的重要挑战，即在肽和蛋白质中特定氨基酸的适度反应速率和反应特异性。这项研究将增强我们对生物环境中化学反应性的基本理解，特别是作为肽序列的函数。研究结果将纳入林博士教授的课程。 该项目将提供跨学科的研究机会，在纽约州立大学布法罗分校的本科生，包括一些来自STEM事业代表性不足的群体，通过与纽约州大学科学和技术入门计划的长期合作。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Qing Lin from State University of New York at Buffalo to use a phage-based method to evolve the alkyne-containing peptides for sequence-specific palladium-mediated cross-coupling reactions with aryl iodide reagents, as well as the cysteine-containing peptides for condensation reactions with nitrile-containing small-molecule probes. By exploiting biological techniques such as phage display, the reactivity of up to 600 billion peptide substrates containing unique chemical functional groups can be interrogated. The effect of the sequence of amino acids on the reactivity of the aforementioned peptides will be studied. The structural basis and mechanism of the two bioorthogonal reactions will be probed using kinetic and nuclear magnetic resonance (NMR) methods. The proposed research seeks to bring new chemical tools to the study of important biological problems. This project addresses important challenges in the development of organic reactions for applications inside living systems, namely the modest reaction rates and specificity of reactions at specific amino acids within peptides and proteins. The research will enhance our fundamental understanding of chemical reactivity in the biological environment, particularly as a function of the sequence of the peptides. The results of the research will be incorporated in courses taught by Dr. Lin. The project will provide interdisciplinary research opportunities to the undergraduate students at State University of New York at Buffalo, including some from the groups underrepresented in STEM careers, through a long-standing collaboration with the New York State Collegiate Science and Technology Entry Program.