细胞中若干糖链介导的识别过程的调控

项目名称： 细胞中若干糖链介导的识别过程的调控

项目编号： No.91213301

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 有机化学

项目作者： 叶新山

作者单位： 北京大学

项目金额： 540万元

中文摘要： 本项目围绕若干糖链介导的细胞识别过程进行研究，包括以下四个方面内容：1）肿瘤细胞中糖链变化的检测及其功能研究；2）糖类化合物对细胞粘附过程的作用和调控研究；3）皂苷类探针的制备及其相关作用靶分子的鉴定；4）糖链加工酶抑制剂对糖链功能的调控。主要发展细胞表面和细胞内肿瘤相关聚糖、糖链加工酶的高灵敏度、高选择性检测新技术和糖基化过程动态监测新方法；运用化学小分子探针，研究糖基化过程对肿瘤相关聚糖表达的影响及对细胞生理行为和下游信号转导过程的调控作用，研究寡糖介导的细胞粘附事件，研究皂苷的药理活性分子机制，研究氮杂糖类化合物的免疫抑制活性机制。本项目的实施，将建立新型基于糖链的疾病诊断方法和治疗靶点，发现药物先导结构，进而为创新药物的发现奠定基础。

中文关键词： 糖；化学探针；分子机制；糖链检测；糖类药物发现

英文摘要： This project will focus the studies on some glycan-mediated cellular recognition processes, including the following contents: 1) the detection of glycan changes in tumor cells and the functions of glycans; 2) the role and modulation of oligosaccharides in cellular adhesion process; 3) the preparation of saponin probes and identification of their action target molecules; 4) the modulation of glycan functions by carbohydrate-processing enzyme inhibitors. We will develop new technologies for highly sensitive and selective detection of tumor-associated glycans and carbohydrate-processing enzymes on cell surface or inside cell, as well as new methods for detection of kinetic glycosylation process. Using small molecule probes, we will investigate the influence on tumor-associated glycan expression during glycosylation process and their modulation of cellular physiological events and downstream signal transduction processes, investigate oligosaccharide-mediated cellular adhesion events, explore the molecular mechanism of biological activities of saponins, and understand the mechanism of iminosugars with immunosuppressive activities. The implement of this project will establish new glycan-based detection methods and therapeutic targets for the treatment of diseases, and find new drug lead compounds, which will benefit t

英文关键词： carbohydrate；chemical probe；molecular mechanism；glycan detection；carbohydrate-based drug discovery