Involvement of water in host-guest interactions.

As predicted by inhibition studies the X-ray crystal structure of the complex formed between the tetrasaccharide alpha-L-Fuc(1----2)-beta-D-Gal(1----3) [alpha-L-Fuc-(1----4)]-beta-D-GlcNAc- OMe (Leb-OMe) and the lectin IV of Griffonia simplicifolia (GS-IV) shows three hydroxyl groups (referred to as the polar key) hydrogen bonded within the combining site and flanked by hydrophobic surfaces. Apart from OH-6 of the beta-D-GlcNAc unit, the six other hydroxyl groups reside at or near the periphery of the combining site. Linear enthalpy-entropy compensation is observed for complex formation with monodeoxy and other derivatives of Leb-OMe involving one of these six hydroxyl groups. Decreases in both the thermodynamic parameters (- delta H 0 and - delta S 0) are largest when a hydroxyl group is in contact with water at the periphery of the combining site. The experimental evidence indicates that the binding reactions involve very similar if not identical changes in the conformations of both the lectin and the ligands; it is therefore proposed that the enthalpy-entropy compensations arise because water molecules hydrogen bonded to the amphiphilic surfaces of the unbound oligosaccharide and the protein are more mobile (higher entropy content) and less strongly hydrogen bonded than are water molecules in bulk solution. Monte Carlo simulations of the hydration of Leb-OMe appear to support this idea. In accordance with this proposal the association of complementary amphiphilic molecular surfaces from aqueous solution is driven by the release of the water molecules from both non-polar and polar regions of the amphiphiles to form stronger hydrogen bonds in bulk water. In the case of highly amphiphilic molecules such as the oligosaccharide Leb-OMe the negative contributions to entropy change dominate positive contributions that may arise from hydrophobic effects. The GS-IV(Leb-OMe)2 complex is stabilized by the hydrogen-bonding networks involving an asparate, an asparagine and a serine residue within the combining site and the above-mentioned key hydroxyl groups. Improved packing of the molecules may also be involved.