CAREER: Novel Reductive Ligations of S-Nitrosothiols

职业生涯：S-亚硝基硫醇的新型还原连接

• 批准号: 0844931
• 负责人: Ming Xian
• 金额: $ 65.66万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0844931&HistoricalAwards=false
• 关键词: CAREER; Novel; Reductive; Ligations; Nitrosothiols

"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.

该奖项是根据2009年美国复苏和再投资法案(公法第111-5条)资助的。该项目旨在为S发现新的化学物质-亚硝硫醇，这是一种重要的一氧化氮代谢物。硫-氮键的不稳定性往往使蛋白质中的S-亚硝硫醇难以准确测定。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-亚硝硫醇转化为稳定的偶联物。初步研究发现了一种新的利用膦-酯底物还原连接S-亚硫醇的方法。它可以在温和的条件下高产率地将S-亚硫醇转化为稳定的亚磺酰胺产品。PI计划进一步优化还原连接，并探索使用磷化氢底物的其他替代连接工艺。还将进行研究，以阐明转化的机制。这些基础研究将促进对S-亚硫醇的化学和生物学性质的了解，并为研究S-亚硫醇在生物系统中与NO信号转导有关的研究奠定基础。凭借这一职业奖，有机与高分子化学项目正在支持华盛顿州立大学化学系冼明教授的研究。西安教授的研究工作围绕着一氧化氮代谢产物的新反应的开发展开。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进取的本科生和研究生提供独特的多学科研究经验。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努力做好更好的准备。