MOLECULAR RECOGNITION .11. THE SYNTHESIS OF EXTENSIVELY DEOXYGENATED DERIVATIVES OF THE H-TYPE-2 HUMAN BLOOD-GROUP DETERMINANT AND THEIR BINDING BY AN ANTI-H-TYPE-2 MONOCLONAL-ANTIBODY AND THE LECTIN-1 OF ULEX-EUROPAEUS

The relative potencies of a wide variety of deoxygenated derivatives of the methyl glycoside of alpha-L-Fuc-(1 --> 2)-beta-D-Gal-(1 --> 4)-beta-D-GlcNAc (the H-type 2 human blood group related trisaccharide) for the inhibition of the binding of an artificial H-type 2 antigen by the lectin I of Ulex europaeus confirmed the previous evidence that the key and productive interaction involves only the three hydroxyl groups of the alpha-L-fucose unit, the hydroxyl at the 3-position of the beta-D-galactose residue, and the nonpolar groups in their immediate environment. Except for the acetamido group and the hydroxymethyl of the beta-D-Gal unit, which stay in the aqueous phase, on complex formation the remaining three hydroxyl groups appear to come to reside at or near the periphery of the combining site since their replacement by hydrogen causes relatively small changes (< +/- 1 kcal/mol) in the stability of the complex (DELTA-G0). Relatively much larger but compensating changes occur for the enthalpy and entropy terms, and these may arise primarily from the differences in the water structure about the periphery of the combining site and the oligosaccharide both prior to and after complexation. It is proposed that steric constraints lead to an ordered state of the water molecules hydrogen-bonded to the polar groups within the cleft formed by the key region of the amphiphilic combining site. Their release to form less ordered clusters of more strongly hydrogen-bonded water molecules in bulk solution would contribute importantly to the driving force for complexation. It is demonstrated that the surface used for the binding of H-type 2-OMe by a monoclonal anti-H antibody is virtually identical to that used by the Ulex lectin.