Optimizing lectin-carbohydrate interactions: Improved binding of divalent alpha-mannosylated ligands towards Concanavalin A

The synthesis and binding properties to Jack bean phytohaemagglutinin in (Concanavalin A, Con A) of a new family of divalent alpha-D-mannopyranoside ligands are described. The synthesis of these ligands is based on the coupling of commercially available diamines to p-isothiocyanatophenyl 2,3,4,6 tetra-O-acetyl-alpha-D-mannopyranoside (4). The resulting dimers 6, 15 to 22 and 30 were tested for their relative inhibitory potency by solid-phase enzyme-linked lectin assays (ELLA) using methyl alpha-D-mannopyranoside as standard. Divalent mannosylated ligand 35 bearing a non-aromatic aglycon was also tested for comparison purposes. Concentrations necessary for 50% inhibition (IC(50)s) of binding of yeast mannan to Jack bean phytohaemagglutinin (Con A) were determined. The inhibitions showed dimers to be approximately 10- to 90-fold more potent than methyl alpha-D-mannopyranoside. Variations in the intra-mannosyl distance proved to be an important factor for optimum binding.