Explore the Chemistry and Chemical Biology of Reactive Sulfur Species

项目总结 探索活性硫物种的化学和化学生物学 活性硫物种(RS)包括硫化氢(H_2S)、过硫化物(RSSH)、 多硫化物(H_2Sn或RSSnR，n≥_2)和半胱氨酸修饰的加合物，如S-亚硝硫醇(SnO)。这些 物种在氧化还原生物学中起着调节作用。它们既是疾病的指示物，也是疾病的执行者。 同时提供诊断和治疗机会。然而，准确的 许多RSS的作用机制仍不清楚。关于以下几个基本问题 我们必须先了解这些物种的化学成分，然后才能期待对生物的了解 和临床应用。我们的实验室发现了RSS的一些有趣的化学和反应。 我们还开发了各种化学工具，可以用来进一步进行生物学研究。 在R35的应用中，我们计划继续努力探索化学和化学生物学 活性硫磺的种类。我们提出了未来五年的四个明确的研究方向：1) 探索新型H_2S/RSS施主和双施主，并研究这些化合物的应用；2) 研究过硫化物与多硫化物的反应，探讨S蛋白的作用机理。 过硫化物供体引起的修饰；3)探索新的H_2S清除系统及其 应用；4)开发下一代基于黄原烯的荧光染料和RSS传感器。 该项目的完成将使我们能够更好地了解它的性质和生物学特性 这些硫磺物种的意义。它还将提供新的研究工具，可用于这两个领域 RSS的基础和转化性生物医学研究。

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.