Explore the Chemistry and Chemical Biology of Reactive Sulfur Species

项目摘要 探索活性硫物种的化学和化学生物学 反应性硫物质（RSS）包括硫化氢（H2S）、过硫化物（RSSH）、 多硫化物（H2Sn或RSSnR，n≥2）和半胱氨酸修饰的加合物，如S-亚硝基硫醇（SNO）。这些 物种在氧化还原生物学中起调节作用。它们既是疾病的指示器，也是疾病的效应器 国家，同时提供诊断和治疗机会。但具体 许多RSS的作用机制仍不清楚。一些基本问题， 在我们期望对这些物种的生物学特性有所了解之前， 和临床应用。我们的实验室已经发现了RSS的一些有趣的化学和反应。 我们还开发了各种化学工具，可用于进一步开展生物学研究。 在这个R35应用程序中，我们计划继续努力探索化学和化学生物学 反应性硫物质。我们提出未来五年的四个研究方向：1） 探索新型H2S/RSS给体和双给体化合物，并研究其应用; 2） 研究过硫化物和多硫化物的反应，并研究蛋白质S- 3）探索新的H2S清除体系及其应用 4）开发下一代基于咕吨的荧光染料和RSS传感器。 该项目的完成将使我们能够更好地了解其性质和生物学特性。 这些含硫物质的重要性。它还将提供新的研究工具，可用于 RSS的基础和转化生物医学研究。

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.