Galectin (GAL,半乳糖凝集素) 能特异性结合半乳糖苷链，通过多价作用形成lattice结构，参与了众多的生理和病理过程。在不同生理环境中，细胞表面的糖链被各种抗原动态修饰，而GAL对不同抗原结构的结合力有显著差异，从而影响lattice的形成，达到动态调控GAL生物功能的目的。由于缺乏有效的研究策略和分析手段，GAL与各类糖链抗原的作用机制及识别模式尚未被系统性研究，阻碍了对GAL生物功能的探索和利用。本项目拟通过化学酶法合成多样化的复杂N-糖链抗原库，通过糖芯片高通量筛选技术获取GAL对各抗原结构的精细识别特异性；结合糖链顺磁探针和STD-NMR技术，在原子水平系统分析GAL与各类复杂N-糖链的作用机制和识别模式，阐明糖基化动态修饰调控GAL生物功能的分子机制；研发的高结合力糖链探针将成为探索GAL生物功能的独特工具，并对相关疾病机制的阐明与新型药物的研发提供新视角及新方案。

By multi-interaction with beta-galactosides to form the lattice on the cell surface, galectins are involved in a wide range of biological and pathological processes. Glycosylation is one of the most important post-translational modifications of proteins and changes dynamically by sialylation, fucosylation and ABO antigen structures. Moreover, galectins show significant difference to these epitopes. However, the fine specificity of galectins to these antigen structures has not been discovered yet. Thus, the mechanism is unclear that how cells regulate the biological functions of galectins by the dynamic glycosylation modification. Here, we propose to systematically study the fine selectivity of galectins by high throughput screening of a library of glycan antigens which will be prepared by chemo-enzymatic synthesis. By combination of Paramagnetic Probe and STD-NMR studies, we will investigate the binding mechanism of galectins to the complex N-glycans at the atomic resolution. The proposal is an advanced multidisciplinary research, including carbohydrate chemistry, glycobiology, cell biology, NMR and glycan microarray. We also will investigate the mechanism of tumor inhibition by the nature ligand to facilitate the tumor treatment.