Development of Sequence-Specific Bioorthogonal Reactions
Qing Lin Principal Investigator
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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. <br/><br/>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.