Divergent Enzymatic Assembly of a Comprehensive 64-Membered IgG N-Glycan Library for Functional Glycomics

  • Adv Sci (Weinh). 2023 Oct;10(30):e2303832. doi: 10.1002/advs.202303832.
Wenjing Ma  1  2 Zhuojia Xu  1  2 Yuhan Jiang  1 Jialin Liu  1 Dandan Xu  3 Wei Huang  1  3 Tiehai Li  1  2
Affiliations
  • 1. State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3. School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou, 310024, China.
Abstract

N-Glycosylation, a main post-translational modification of Immunoglobulin G (IgG), plays a significant role in modulating the immune functions of IgG. However, the precise function elucidation of IgG N-glycosylation remains impeded due to the obstacles in obtaining comprehensive and well-defined N-glycans. Here, an easy-to-implement divergent approach is described to synthesize a 64-membered IgG N-glycan library covering all possible biantennary and bisected N-glycans by reprogramming biosynthetic assembly lines based on the inherent branch selectivity and substrate specificity of Enzymes. The unique binding specificities of 64 N-glycans with different proteins are deciphered by glycan microarray technology. This unprecedented collection of synthetic IgG N-glycans can serve as standards for N-glycan structure identification in complex biological samples and the microarray data enrich N-glycan glycomics to facilitate biomedical applications.

Keywords
IgG N-glycan library; carbohydrates; enzyme-catalyzed synthesis; functional glycomics; glycan microarray.