含α(2,8)三唾液酸结构单元的神经节苷脂GT3的全合成、荧光标记与细胞膜探针研究

项目名称： 含α(2,8)三唾液酸结构单元的神经节苷脂GT3的全合成、荧光标记与细胞膜探针研究

项目编号： No.21272027

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 邢国文

作者单位： 北京师范大学

项目金额： 80万元

中文摘要： 神经节苷脂GT3是在乳腺癌细胞膜表面过量表达的一种肿瘤相关糖类抗原。其分子结构中含有α(2,8)三唾液酸结构单元，是一种结构复杂的酸性鞘糖脂。由于GT3分子的复杂性，对其进行化学全合成具有很高的挑战性。本项目将在课题组以往唾液酸化学和荧光检测研究的基础上开展神经节苷脂GT3的化学生物学研究。我们将发展反应活性、糖苷化产率、α立体选择性俱佳的新型唾液酸亚砜苷糖基给体，一釜合成法构建α(2,8)三唾液酸结构单元，实现神经节苷脂GT3的全合成；设计合成新型基于鏻盐的高灵敏、强荧光的染料分子，制备各种类型的GT3荧光标记物；探究其作为细胞膜探针在肿瘤细胞研究中的应用，期望从分子水平上对深入阐释肿瘤的发病机制提供有益帮助。本课题的开展将为复杂唾液酸糖缀合物的合成与生物活性研究提供强有力的支持，有效促进唾液酸化学和生物学相关研究领域的发展，具有重要的理论价值和广阔的应用前景。

中文关键词： 唾液酸；糖苷化；荧光探针；细胞成像；

英文摘要： Ganglioside GT3 is a kind of tumor-associated carbohydrate antigen, which is over expressed on the surface of breast cancer cell. GT3 is a complex acidic glycosphingolipid bearing α(2,8) trisialic acid moiety in its structure. It is high challengeable to achieve the total synthesis of GT3 due to its molecular complexity. Based on our previous study on sialic acid chemistry and fluorescent detection, herein, we will perform the chemical biology research of ganglioside GT3. Firstly, the project will focus on the development of novel sialyl sulfoxide donors with good reactivity, high glycosylation yield and excellent α-selectivity, and construct α(2,8) trisialic acid moiety by one-pot synthetic strategy to accomplish the total synthesis of GT3. Secondly, we will design and synthesize new phosphonium-based dyes with high sensitivity and strong fluorescence, and prepare various types of GT3 fluorescent markers. Thirdly, the proposal will explore the possibilities in cancer cell study with GT3 fluorescent markers as cell membrane sensors, which would be helpful for the understanding of cancer pathogenesis at molecular level. This project will give powerful supports to the synthesis and biological study of complex sialylconjugates, efficiently to accelerate the development of sialic acid chemistry, biology and rela

英文关键词： sialic acid；glycosylation；fluorescent probe；cell imaging；