Chemical Tools for Understanding the Redox Biology of Reactive Sulfur Species

了解活性硫物质氧化还原生物学的化学工具

• 批准号: 10082454
• 负责人: Ming Xian
• 金额: $ 33.74万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082454
• 关键词: Address; Biological; Biological Assay; Biology; Cell model; Cells; Chemicals; Chemistry; Clinical; Collaborations; Cysteine; Cytoprotection; Detection; Disease; Effectiveness; Family; Fluorescence; Fluorescent Probes; Future; Generations; Goals; Hydrogen; Hydrogen Sulfide; Image; Label; Laboratories; Mass Spectrum Analysis; Measures; Mediating; Methods; Modification; Nitrogen; Oxidation-Reduction; Oxidative Stress; Oxygen; Pacific Northwest; Pathologic; Pathology; Pathway interactions; Pharmacology; Physiological; Physiology; Play; Post-Translational Protein Processing; Protein S; Proteins; Proteome; Proteomics; Protocols documentation; Reaction; Reagent; Regulation; Research; Role; Sampling; Series; Signal Transduction; Signaling Molecule; Stress; Sulfur; System; Testing; Therapeutic; Tissues; base; biological systems; clinical application; detection method; drug discovery; imaging probe; member; novel; persulfides; polysulfide; protein profiling; small molecule; sulfhydration; tool; Address; Biological; Biological Assay; Biology; Cell model; Cells; Chemicals; Chemistry; Clinical; Collaborations; Cysteine; Cytoprotection; Detection; Disease; Effectiveness; Family; Fluorescence; Fluorescent Probes; Future; Generations; Goals; Hydrogen; Hydrogen Sulfide; Image; Label; Laboratories; Mass Spectrum Analysis; Measures; Mediating; Methods; Modification; Nitrogen; Oxidation-Reduction; Oxidative Stress; Oxygen; Pacific Northwest; Pathologic; Pathology; Pathway interactions; Pharmacology; Physiological; Physiology; Play; Post-Translational Protein Processing; Protein S; Proteins; Proteome; Proteomics; Protocols documentation; Reaction; Reagent; Regulation; Research; Role; Sampling; Series; Signal Transduction; Signaling Molecule; Stress; Sulfur; System; Testing; Therapeutic; Tissues; base; biological systems; clinical application; detection method; drug discovery; imaging probe; member; novel; persulfides; polysulfide; protein profiling; small molecule; sulfhydration; tool

PROJECT SUMMARY Reactive sulfur species such as persulfides (RSSH) and hydrogen polysulfides (H2Sn) play regulatory roles in redox biology. Modulation of their cellular levels could have potential therapeutic value. However, their exact mechanisms of action are still unclear. A number of fundamental questions concerning the chemistry of these species must be addressed before we can expect a biological understanding or clinical applications. It is vital to understand the reactivity of these species and to appreciate the limitation and errors that may be generated when measuring them in biological samples. In this context, research tools for accurate and convenient detection of these sulfur species are urgently needed. Our lab has recently discovered some unique chemistry and reactions of RSSH and H2Sn. Based on these discoveries, we expect that highly sensitive and specific chemical tools for the study of RSSH and H2Sn can be developed. We also expect these tools will enable us to better understand the biological significance of RSSH and H2Sn. In this application, we plan to pursue three specific aims: 1) to develop new RSSH generation methods and labeling strategies for quantitative proteomics characterization of protein S-sulfhydration, 2) to establish new chemistry and imaging probes for hydrogen polysulfides; 3) to assess the distinctive contribution of reactive sulfur species on protein S-sulfhydration and its implications on stress regulation. The proposed research will allow us to establish novel reagents and protocols for generating specific types of reactive sulfur species, new probes for imaging such species, and optimized quantitative proteomics approaches for effective profiling of protein posttranslational modifications impacted by reactive sulfur species.

项目摘要 反应性硫种类，例如硫化物（RSSH）和氢多硫化物（H2SN） 氧化还原生物学中的调节作用。调节其细胞水平可能具有潜在的治疗性 价值。但是，它们的确切作用机制仍然不清楚。许多基本 关于这些物种化学反应的问题必须在我们期望 生物学理解或临床应用。了解这些物种的反应性至关重要 并欣赏在生物学中测量它们时可能产生的限制和错误 样品。在这种情况下，用于准确和方便检测这些硫的研究工具 迫切需要。我们的实验室最近发现了RSSH的一些独特的化学和反应 和H2SN。基于这些发现，我们希望高度敏感和特定的化学工具用于 可以开发对RSSH和H2SN的研究。我们还希望这些工具将使我们能够更好 了解RSSH和H2SN的生物学意义。在此应用程序中，我们计划追求三个 具体目的：1）开发新的RSSH生成方法和标签策略以定量 蛋白质S-硫化的蛋白质组学表征，2）建立新的化学和成像 氢多硫化物的探针； 3）评估反应性硫物种对 蛋白质S-硫化及其对压力调节的影响。拟议的研究将使我们 为了建立新的试剂和方案来产生特定类型的反应性硫物种，新的 用于成像此类物种的探针，并优化了定量蛋白质组学方法以有效 受反应性硫物种影响的蛋白质翻译后修饰的分析。