Emerging Principles for the Therapeutic Exploitation of Glycosylation

Glycosylation plays a key role in a wide range of biological processes. Specific modification to a glycan’s structure can directly modulate its biological function. Glycans are not only essential to glycoprotein folding, cellular homeostasis, and immune regulation but are involved in multiple disease conditions.

Antibody glycosylation determines Fc functions. An example is the removal of an antibody’s Fc glycans (red, green, and blue) by a bacterial immune evasion factor, endoglycosidase S, which impedes Fc engagement with cellular receptors (orange) and therefore immunological effector cells.

An increased molecular and structural understanding of the mechanistic role that glycans play in these pathological processes has driven the development of therapeutics and illuminated novel targets for drug design. This knowledge has enabled the treatment of metabolic disorders and the development of antivirals and shaped cancer and viral vaccine strategies. Furthermore, an understanding of glycosylation has led to the development of specific drug glycoforms, for example, monoclonal antibodies, with enhanced potency. This article summarizes important advances and ongoing research in the field of glycobiology that will interest readers working in several therapeutic areas.