Molecular recognition. III. The binding of the H-type 2 human blood group determinant by the lectin I of Ulexeuropaeus

Abstract

Using a radioimmunoassay to measure the relative potencies of a wide range of chemically modified structures related to the H-type 2 human blood group determinant, evidence was accumulated that the binding of αLFuc(1→2)βDGal(1→4)-βDGlcNAc-OMe by the lectin I of Ulexeuropaeus involves a wedge-shaped amphiphilic surface which extends on one side of the molecule from the methoxy aglycon to OH-3 of the βDGal unit. A cluster which involves OH-3, OH-4, and OH-2 of the αLFuc unit along with OH-3 of the βDGal unit provides the polar interactions with the lectin. However, only OH-3 and OH-4 of the αLFuc are indispensable to complex formation and are regarded as providing the key polar interaction. The binding reaction involves both a decrease in enthalpy of 29 kcal/mol and a decrease of 68 cal/mol/K in entropy. It is submitted that the main source of the decrease in enthalpy is the establishment of nonpolar interactions that extend from the aglycon over the nonpolar portion of the β-side of the βDGlcNAc unit and on to include a major portion of the α-side of the αLFuc unit. The binding of the βDGlcNAc unit includes OH-6 intramolecularly hydrogen bonded to O-5 in order to extend the nonpolar interactions to the α-side of this unit and perhaps beyond. The decreases in enthalpy (6.0 kcal/mol) and entropy (2.7 cal/mol/K) which occur on the binding of methyl α-L-fucopyranoside are much smaller than for the H-type 2 trisaccharide and are compatible with the much smaller surface that interacts to form the complex. The inhibition data obtained using a range of structures related to methyl α-L-fucopyranoside are in general accord with expectations based on the results obtained with the more complex structures.