Thermodynamic analysis of the binding of galactose and poly-N-acetyllactosamine derivatives to human galectin-3.

Galectin-3, with a wide tissue distribution and marked developmental regulation, provides significant insights into the progression of various disease and developmental stages. Recognized by its specificity for galactose, a detailed characterization of its sugar binding ability has been investigated by isothermal titration calorimetry. The results presented here complement well with the earlier studies utilizing hapten inhibition assays. Among the various lactose derivatives studied, A-tetrasaccharide emerged with the highest affinity for binding to galectin-3 combining site. This blood group saccharide exhibited a binding affinity 37-fold higher and a 102 kJ/mol more favorable change in enthalpy over lactose at 280 K indicating the existence of additional subsites for both the alpha1-3-linked N-acetylgalactosamine at the non-reducing end and the alpha1-2-linked L-fucosyl residue. The thermodynamic parameters evaluated for other ligands substantiate further the carbohydrate recognition domain to be part of an extended binding site. Binding thermodynamics of galectin-3 with the galactose derivatives are essentially enthalpically driven and exhibit compensatory changes in DeltaH degrees and TDeltaS owing to solvent reorganization.