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

基本信息

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
项目类别：
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

项目摘要

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。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Specific Reactions of RSNO, HSNO, and HNO and Their Applications in the Design of Fluorescent Probes.

DOI：
10.1002/chem.202001885
发表时间：
2020-09-10
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
0
作者：
Wang Y;Xu S;Xian M
通讯作者：
Xian M

Shining a light on SSP4: A comprehensive analysis and biological applications for the detection of sulfane sulfurs.

DOI：
10.1016/j.redox.2022.102433
发表时间：
2022-10
期刊：
REDOX BIOLOGY
影响因子：
11.4
作者：
Shieh, Meg;Ni, Xiang;Xu, Shi;Lindahl, Stephen P.;Yang, Moua;Matsunaga, Tetsuro;Flaumenhaft, Robert;Akaike, Takaaki;Xian, Ming
通讯作者：
Xian, Ming

Phosphite Esters: Reagents for Exploring S-Nitrosothiol Chemistry.

亚磷酸酯：探索 S-亚硝基硫醇化学的试剂。