CAREER: Novel Reductive Ligations of S-Nitrosothiols

“这项奖励是根据2009年美国复苏和再投资法案（公法111-5）资助的。”该项目旨在发现s -亚硝基硫醇的新化学成分，这是一种重要的一氧化氮代谢物。硫氮键的不稳定性使得精确测量蛋白质中的s -亚硝基硫醇变得很麻烦。在这个项目中，PI计划开发新的反应，可以选择性地将不稳定的s -亚硝基硫醇转化为稳定的偶联物。初步研究发现了一种利用膦酸酯底物还原连接s -亚硝基硫醇的新方法。在温和条件下，s -亚硝基硫醇可高产、稳定地转化为亚砜酰胺产品。PI计划进一步优化还原性连接并探索使用膦基底物的其他替代连接过程。还将进行研究以阐明这种转变的机制。这些基础研究将促进对s -亚硝基硫醇的化学和生物学特性的理解，并允许研究s -亚硝基硫醇在生物系统中相关的NO信号转导。有机和大分子化学项目通过该职业奖支持华盛顿州立大学化学系明献教授的研究。冼教授的研究工作围绕着开发一氧化氮代谢物的新反应。预计这些反应将具有变革性，有可能影响自由基生物学。此外，该项目的教育部分将为积极进取的本科生和研究生提供多学科研究的独特体验。它将把这些年轻人带到实验室，让他们第一次接触科学研究，并为他们未来在科学领域的努力做好更好的准备。

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)".This project is directed toward the discovery of new chemistry for S-nitrosothiols, which are important nitric oxide metabolites. The lability of the sulfur-nitrogen bonds often makes S-nitrosothiols in proteins cumbersome to measure accurately. In this project, the PI plans to develop new reactions that can selectively convert unstable S-nitrosothiols to stable conjugates. Preliminary studies have uncovered a new reductive ligation of S-nitrosothiols using phosphine-ester substrates. It can convert S-nitrosothiols to stable sulfenamide products in high yields under mild conditions. The PI plans to further optimize the reductive ligation and explore other alternative ligation processes using phosphine-based substrates. Studies to elucidate the mechanisms of the transformation will also be performed. These fundamental studies will advance the understanding of the chemical and biological properties of S-nitrosothiols and permit studies of S-nitrosothiol related NO signal transduction in biological systems. With this CAREER award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Ming Xian of the Department of Chemistry at Washington State University. Professor Xian's research efforts revolve around the development of new reactions of nitric oxide metabolites. These reactions are expected to be transformative, with the potential to impact free radical biology. In addition, the education portion of this project will provide a unique experience in multidisciplinary research for highly motivated undergraduate and graduate students. It will bring those young people into the laboratory for their first encounter with scientific research and better prepare them for their future endeavors in science.