Bridging lectin binding sites by multivalent carbohydrates

Carbohydrate-protein interactions are involved in a multitude of biological recognition processes. Since individual protein-carbohydrate interactions are usually weak, multivalency is often required to achieve biologically relevant binding affinities and selectivities. Among the possible mechanisms responsible for binding enhancement by multivalency, the simultaneous attachment of a multivalent ligand to several binding sites of a multivalent receptor (i.e. chelation) has been proven to have a strong impact. This article summarizes recent examples of chelating lectin ligands of different size. Covered lectins include the Shiga-like toxin, where the shortest distance between binding sites is ca. 9 angstrom, wheat germ agglutinin (WGA) (shortest distance between binding sites 13-14 angstrom), LecA from Pseudomonas aeruginosa (shortest distance 26 angstrom), cholera toxin and heat-labile enterotoxin (shortest distance 31 angstrom), anti-HIV antibody 2G12 (shortest distance 31 angstrom), concanavalin A (ConA) (shortest distance 72 angstrom), RCA(120) (shortest distance 100 angstrom), and Erythrina cristagalli (ECL) (shortest distance 100 angstrom). While chelating binding of the discussed ligands is likely, experimental proof, for example by X-ray crystallography, is limited to only a few cases.