Explore the Chemistry and Chemical Biology of Reactive Sulfur Species

PROJECT SUMMARY Explore the Chemistry and Chemical Biology of Reactive Sulfur Species Reactive sulfur species (RSS) include hydrogen sulfide (H2S), persulfides (RSSH), polysulfides (H2Sn or RSSnR, n≥2), and cysteine-modified adducts like S-nitrosothiols (SNO). These species play regulatory roles in redox biology. They are both indicators and effectors of disease states, simultaneously offering diagnostic and therapeutic opportunities. However, the exact mechanisms of action of many RSS are still unclear. A number of fundamental questions concerning the chemistry of these species must be addressed before we can expect a biological understanding and clinical applications. Our lab has discovered some interesting chemistry and reactions of RSS. We have also developed a variety of chemical tools that can be used to further their biological studies. In this R35 application we plan to continue our efforts on exploring the chemistry and chemical biology of reactive sulfur species. We propose four distinct research directions for the next five years: 1) to explore novel H2S/RSS donors and dual donors, and to study the applications of these compounds; 2) to study the reactions of persulfides and polysulfides, and to investigate mechanisms of protein S- modifications caused by persulfide donors; 3) to explore novel H2S scavenging systems and their applications; 4) to develop the next generation of xanthene-based fluorescent dyes and RSS sensors. The completion of this project will allow us to better understand the properties and biological significance of these sulfur species. It will also provide novel research tools that can be used in both basic and translational biomedical research on RSS.