Molecular recognition. VIII. The binding of the β-D-galactopyranosyl residue of the Lewis b human blood group determinant by the lectin IV of Griffonia simplicifolia and by a monoclonal anti-Lewis b antibody. Evidence for intramolecular hydrogen bonding

Abstract

The 3b-deoxy, 4b-deoxy, 6b-deoxy, 6b-deoxy-6b-fluoro, 6b-chloro-6b-deoxy, and the 5b-des-hydroxymethyl derivatives of the Lewis b (αLFucd(1 → 2)βDGalb(1 → 3)[αLFucc(1 → 4)]βDGlcNAca-OMe) human blood group determinant were synthesized in order to examine the involvement of the βDGal b unit in the binding of the Leb-OMe tetrasaccharide both by the lectin IV of Griffonia simplicifolia and a hybridoma monoclonal anti-Leb antibody. The replacement of the CH2OH-5b group by hydrogen resulted in very weak binding by both the proteins, but the 6b-deoxy derivative was bound nearly as strongly as the parent compound in the case of the lectin but nine times more strongly in the case of the antibody. The 6b-fluoride was slightly more strongly bound than the 6b-deoxy derivative by both the proteins. On the other hand, the 6b-chloride was bound three times more strongly by the lectin but three times more weakly by the antibody than the 6b-deoxy derivative. The thermodynamic parameters for the binding of the 6b-deoxy derivative by the lectin as compared to those for Leb-OMe confirmed that OH-6b interacts within the combining site of the complex. The results appear to require that for both proteins the CH2OH-5b group becomes involved in nonpolar interactions within the combining site. It seems probable that OH-6b is accepted intramolecularly hydrogen bonded to O-5b in the case of the lectin but to OH-4b in the case of the antibody. The involvement of OH-3b, OH-4b, and OH-4c as the key polar grouping for the binding of Leb-OMe by the lectin and of OH-3b and OH-2d in the case of the antibody was reported previously.