CAREER: Novel Reductive Ligations of S-Nitrosothiols

“该奖项是根据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，S-亚硝基硫醇是重要的一氧化氮代谢物。硫-氮键的不稳定性通常使蛋白质中的S-亚硝基硫醇难以准确测量。 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共轭物。初步研究发现了一个新的还原连接S-亚硝基硫醇使用膦酯底物。 它可以在温和的条件下以高产率将S-亚硝基硫醇转化为稳定的次磺酰胺产物。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转化的机制。这些基础研究将推进对S-亚硝基硫醇的化学和生物学性质的理解，并允许在生物系统中研究S-亚硝基硫醇相关的NO信号转导。 有了这个CAREER奖，有机和高分子化学计划支持华盛顿州立大学化学系教授Ming Xian的研究。冼教授的研究工作围绕着一氧化氮代谢产物的新反应的发展。这些反应预计将是变革性的，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性高的本科生和研究生提供多学科研究的独特经验。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，并为他们未来的科学事业做好更好的准备。

"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.