GlycoMimetics

Glycomimetics are chemical compounds designed to mimic the structure, stereochemistry, and biological activity of carbohydrates. They aim to engage carbohydrate-binding proteins (lectins) and carbohydrate-processing enzymes in ways that native sugars do not, often to improve stability, selectivity, or pharmacokinetic properties.

Many glycomimetics replace glycosidic linkages with non-hydrolyzable analogs such as C-glycosides or S-glycosides, or use conformationally constrained sugar mimics like azasugars and cyclitol derivatives. Non-saccharide scaffolds can display analogous spatial arrangements of hydroxyl groups to approximate sugar recognition. Multivalent displays, wherein multiple glycomimetic units are presented on a polymer, dendrimer, or nanoparticle, exploit the clustered binding frequently observed in lectin–carbohydrate interactions. Improved bioavailability can be achieved by increasing lipophilicity or introducing stability against glycosidases, and by tuning physicochemical properties to enable oral administration.

Glycomimetics have been developed as inhibitors of glycosidases and glycosyltransferases, as ligands or antagonists for lectins, and as mimics of glycosaminoglycans such as heparan sulfate. They are studied for therapeutic applications in cancer, infectious diseases, inflammation, and for diagnostics and imaging. In research, they serve as tools to probe carbohydrate recognition networks and to dissect cell-surface interactions.

Challenges include achieving high selectivity for a given protein, avoiding off-target binding, achieving favorable pharmacokinetics, ensuring synthetic accessibility and scalable production, and navigating regulatory approval for non-carbohydrate mimetics. The field integrates medicinal chemistry, carbohydrate chemistry, structural biology, and materials science to design effective glycomimetics.