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 (IC50s) 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.
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Department of Chemistry, University of Ottawa, ON, Canada.
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D001665:Binding Sites; D001667:Binding, Competitive; D003208:Concanavalin A / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D009904:Optical Rotation; D013329:Structure-Activity Relationship
D008024:Ligands; D008362:Mannosides; D003208:Concanavalin A