Explore the Chemistry and Chemical Biology of Reactive Sulfur Species

探索活性硫物质的化学和化学生物学

• 批准号: 10611045
• 负责人: Ming Xian
• 金额: $ 39.88万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611045
• 关键词: Address; Biological; Biology; Biomedical Research; Chemicals; Chemistry; Clinical; Cysteine; Detection; Diagnostic; Disease; Fluorescent Dyes; Generations; Hydrogen; Hydrogen Sulfide; Oxidation-Reduction; Physiological; Play; Post-Translational Protein Processing; Property; Reaction; Research; Role; S-Nitrosothiols; Sulfur; System; Therapeutic; Xanthenes; adduct; clinical application; next generation; novel; persulfides; polysulfide; programs; sensor; tool

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.

项目概要 探索活性硫物质的化学和化学生物学 活性硫物质 (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)。 物种在氧化还原生物学中发挥调节作用，它们既是疾病的指标又是疾病的效应器。 状态，同时提供诊断和治疗机会。 许多 RSS 的作用机制仍不清楚。 在我们期望获得生物学上的理解之前，必须先解决这些物种的化学问题 我们的实验室发现了 RSS 的一些有趣的化学和反应。 我们还开发了多种化学工具，可用于进一步进行生物学研究。 在这个 R35 应用中，我们计划继续努力探索化学和化学生物学 我们提出了未来五年的四个不同的研究方向：1） 探索新型H2S/RSS供体和双供体，并研究这些化合物的应用2)； 研究过硫化物和多硫化物的反应，并研究蛋白质 S- 的机制 过硫化物供体引起的修饰；3）探索新型H2S清除系统及其 应用；4）开发下一代基于呫吨的荧光染料和RSS传感器。 这个项目的完成将使我们更好地了解其特性和生物学 这些硫物质的重要性还将提供可用于这两个领域的新颖的研究工具。 RSS 的基础和转化生物医学研究。