高选择性细胞表面蛋白质相邻巯基荧光探针的设计、合成与原位荧光成像研究

项目名称： 高选择性细胞表面蛋白质相邻巯基荧光探针的设计、合成与原位荧光成像研究

项目编号： No.21302125

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 黄楚森

作者单位： 上海师范大学

项目金额： 25万元

中文摘要： 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。是蛋白质上最具有反应活性的基团，它们在氧化还原应激中通过与二硫键的可逆转换，广泛参与了细胞内的信号转导，与心血管、肿瘤、糖尿病、神经退化等许多重要疾病密切相关。最新研究表明细胞表面（细胞外膜）的相邻巯基蛋白直接参与了艾滋病毒(HIV)入侵正常细胞和各类炎症的调控。然而长期以来，蛋白质相邻巯基的直接、专一和快速检测手段缺乏，尤其是用于原位成像的小分子荧光探针几乎没有，限制了该领域的发展。本项目在原先研究基础上，进一步优化设计与合成用于选择性检测细胞表面蛋白质相邻巯基的小分子荧光标记探针，集中于建立活细胞表面相邻巯基蛋白原位荧光成像技术，实现活细胞表面蛋白质相邻巯基的可视化、动态跟踪。本项目的完成将为揭示细胞表面蛋白质相邻巯基在氧化还原信号转导过程中所起的作用提供新的荧光成像技术，为发现与筛选新的药物靶标和相关疾病早期诊提供新的工具与思路。

中文关键词： 荧光探针；蛋白质相邻巯基；荧光成像；细胞表面；氧化还原

英文摘要： Protein vicinal dithiols are closely spaced sulfhydryl groups that exist in native proteins. Vicinal dithiols are the most reactive moiety and found in regulation of cellular signal transduction through the reversible dithiol/disulfide conversions during the redox stimulation. They correlated with many important diseases such as cadiovascular diseases,cancer,diabetes and neurodegenerative diseases. Recent study suggested that cell-surface vicinal- dithiol-containing proteins (csVDPs) have participated in regulation of human immunodeficiency virus (HIV) invasion and various imflammation. However, there is a limitation in this field due to no versatile, specific and rapid tools, especially no small-molecule fluorescent probes developed for in situ image of proten vicinal dihtiols. This project will design highly selective fluorescent probes for specific trapping csVDPs based on our previous work. And focus on the development of the in situ fluorescence imaging techniques for dynamic tracing of vicinal dithiols on csVDPs in living cells. The results of this project will afford a novel fluorescent technology that can be applicable to further studying the significant roles of cell-surface protein vicinal dithiols in redox signal transduction, and searching for new drug targets and earlier diagnosis of related diseas

英文关键词： fluorescent probe；protein vicinal dithiols；fluorescent imaging；cell surface；redox