CAREER: Novel Reductive Ligations of S-Nitrosothiols

Washington State University, Pullman WA

Investigators

Abstract

"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.