Sugarbinding

Sugarbinding describes the molecular recognition events in which a sugar molecule, or a derivative such as a glycan, binds to a complementary binding partner. In biology, sugarbinding is mediated by carbohydrate-binding proteins such as lectins and by specialized binding domains in enzymes and receptors. The term covers both monosaccharide and complex glycan interactions, including interactions on cell surfaces and in extracellular matrices.

Binding is driven by hydrogen bonds between sugar hydroxyls and amino acid residues, electrostatic contacts with acidic residues or metal ions, van der Waals contacts, and sometimes hydrophobic contacts with nonpolar faces of sugars. The three-dimensional arrangement of hydroxyl groups largely determines which sugars are recognized; many interactions are highly specific for particular monosaccharides or glycosidic linkages. Because sugars are often presented in multiple copies on a molecule or cell surface, multivalency can greatly increase apparent affinity and avidity.

Well-known sugar-binding proteins include galectins that recognize beta-galactosides; selectins that bind sialylated and fucosylated glycans during leukocyte trafficking; siglecs that recognize sialic acids; and various bacterial adhesins that attach to host glycans. Carbohydrate-binding modules, found in many glycoside hydrolases, confer substrate targeting. Chemists also develop synthetic sugar-binding ligands, such as boronic acids, capable of forming reversible complexes with diol-containing sugars.

Biologically, sugarbinding mediates cell-cell adhesion, immune recognition, pathogen binding, and glycoprotein trafficking. In biotechnology, sugar-binding proteins enable glycan analysis, affinity purification, and microarrays; structural methods (X-ray crystallography, NMR) and biophysical techniques (ITC, SPR) quantify affinities and specificities.

Understanding sugarbinding is complicated by microheterogeneity of glycans and context-dependent presentation; however it remains central to glycobiology and has potential in diagnostics and therapeutics.