CARB 23 |
| The utility of carbohydrates as therapeutic agents is frustrated by the low affinity of monovalent carbohydrate ligands for their protein receptors. Most carbohydrate binding proteins exist in vivo as multimeric assemblies containing between two and five discrete binding sites. This observation suggests that Nature overcomes the ‘weak binding' problem through multivalency, binding several carbohydrate epitopes simultaneously. From this premise, myriad multivalent carbohydrate ligands have been prepared and bound to a wide range of lectin targets. Most – if not all –bind preferentially in an intermolecular fashion, leading to aggregation and precipitation. Many non-saccharide multivalent ligands that could bind in an intermolecular fashion bind instead in an intramolecular fashion, leading to high affinity in the traditional sense of the term. We have examined the binding of a range of multivalent systems calorimetrically. The derived thermodynamic parameters are interpreted in a Jencksian additivity model to shed light on the molecular origin of additivity in ligand binding. |
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Carbohydrate Recognition Mechanisms and Applications
2:00 PM-4:40 PM, Tuesday, 28 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |