蛋白质相邻巯基是指在空间上邻近的一对或多对蛋白质巯基。通过与二硫键的可逆转换，它们广泛参与了氧化还原信号转导过程。最新研究表明生物体内蛋白质相邻巯基直接参与各类炎症和肿瘤微环境内氧化还原的调控。然而长期以来，用于蛋白质相邻巯基动态可视化成像和定量检测的直接、高效检测方法几乎没有，限制了该领域的发展。本项目在原先研究基础上，优化设计与合成用于活细胞内动态跟踪蛋白质相邻巯基的“off-on”型和比值型荧光探针，建立活细胞内蛋白质相邻巯基动态荧光成像技术和精确定量检测。在此基础上，进一步开展活体（斑马鱼胚胎和小鼠模型）中炎症和肿瘤微环境蛋白质相邻巯基的动态可视化成像和定量检测研究。阐明在氧化还原应激下，炎症和肿瘤组织中蛋白质相邻巯基的动态变化。本项目的完成将为揭示蛋白质相邻巯基操纵的生物体内炎症和肿瘤微环境检测提供新的荧光成像技术，为发现与筛选新的炎症药物靶标和肿瘤早期诊断提供新的工具与思路。

Protein vicinal dithiols are closely spaced sulfhydryl groups that exist in native proteins. Vicinal dithiols are found in regulation of cellular signal transduction through the reversible dithiol/disulfide conversions during the redox stimulation. Recent study suggested that protein vicinal dithiols have participated in regulation of various inflammation and redox homeostasis of tumor microenvironment. However, there is a limitation in this field due to no versatile and effective tools developed for dynamic tracing and quantitative detection of protein vicinal dithiols. This project will design the “off-on” and ratiometric fluorescent probes for dynamic tracing and quantitative detection of the protein vicinal dithiols based on our previous work. And focus on developing the techniques for noninvasive dynamic fluorescence imaging and quantitative determination of endogenous protein vicinal dithiols in live cells under redox stimulation. By using these fluorescence techniques, we will further investigate the dynamic changes of protein vicinal dithiols in inflammatory part and tumor microenvironment of model animals (such as zebrafish and mouse). The results of this project will afford a novel fluorescent technology that can be applicable to further studying the significant roles of protein vicinal dithiols in regulating the inflammation and tumor microenvironment, and searching for new drug targets of inflammation as well as providing new tools for earlier diagnosis of cancer.