抗体糖基化结构对抗体的生物学功能起到至关重要的作用，控制糖链结构来调节抗体活性被称为糖工程抗体。糖工程抗体与抗体药物偶联物(ADC)作为新一代抗体药物已经成为研发的热点。我们前期研究中初步建立了酶催化抗体糖基化改造技术，用于制备药效优化的糖工程抗体。本课题旨在运用化学方法改造生物大分子，探索精确糖链结构对抗体生物学活性的影响；系统性发展和完善一套新颖的糖苷酶催化抗体N-糖链修饰的方法，利用“一锅法”制备的N-糖链底物库，突破精确糖链结构抗体难以制备的局限，筛选糖基化优化的糖工程抗体；同时在酶催化糖基化反应中在糖链上定点引入特殊官能团，利用相应的生物兼容反应偶联小分子细胞毒药物，实现基于抗体糖链的ADC定点定量偶联方法的创新。

Antibody glycosylation is crucial for its bioligical functions. A glycoengineered antibody is to manipulate the strucutres of N-glycans for better activity. As the new generation antibody drugs, glycoengineered antibody and antibody drug conjugates (ADC) have become the reserach focus in pharmceutical industry. In our preliminary research, we have established an enzymatic glycosyaltion technology for preparation of glycoengineered antibodies. In current project, our major goal is to chemically manipulate bio-molecules and explore the role of detailed glycan structure in antibody activity. We sought to develop and improve the novel technology of enzymatic glycosylation modification of antibody using N-glycan substrate library prepapred via a "one-pot" approach to break through the production limit of fine glycan structure antibodies and to screen for better activity. Meanwhile, functional groups were introduced onto glycans via the enzymatic glycosylation for site-specific conjugation with small-molecule cytotoxic drugs by bioorthogonal methods. This present an innovative approach for ADC site-specific and quantitative conjugation based on antibody glycans.