Using Synthetic Glycans to Investigate Anti‐Glycan Antibodies and Explore Their Medical Potential

The dynamic glycan layer that surrounds human and microbial cells plays an essential role in the immune system's capacity to maintain immune tolerance and equilibrium, fight pathogens and cancer. Endogenous anti-glycan antibodies are an indispensable part of immune surveillance, identifying abnormal microbial glycans, viral glycoproteins, and altered tumor-associated carbohydrate antigens. These glycans serve in turn as attractive targets for passive and active immunization strategies in a range of human diseases. The enormous complexity and structural diversity of glycans has made it very difficult to unlock their full biomedical potential. Recent advances in glycan synthesis, including automated solid-phase assembly, chemoenzymatic strategies, and one-pot approaches, enabled unprecedented access to well-defined, homogenous structures. Hence, synthetic glycans of increasing structural complexity pave the way for a range of applications, from profiling endogenous antibody repertoires for biomarker discovery to therapeutic antibody development and vaccine design. Here, we summarize the strategies to utilize synthetic glycans for antibody development and their application in basic research and translational medicine. We outline how anti-glycan antibodies are utilized for diagnostic and therapeutic purposes, while emphasizing the power of synthetic glycans and highlighting their potential in personalized medicine.