Molecular recognition. V. The binding of the B human blood group determinant by hybridoma monoclonal antibodies

Abstract

A systematic study was made of the effect of changes in the structure of αLFuc(1→2)[αDGal(1→3)]βDGal-OMe (1) on the inhibition of the binding of an artificial antigen by two monoclonal anti-B antibodies. Both OH-4 of the βDGal unit and OH-2 of the αDGal unit are essential for binding by one of the antibodies. For the other antibody, OH-3 of the αDGal unit also forms part of the key polar grouping. Both the antibodies recognize a large lipophilic surface extending from the CH3-6 group of the αLFuc unit along the α-sides of this group and the βDGal unit to include its CH2OH-6 group, most likely intramolecularly hydrogen bonded to the neighboring O-5. The lipophilic surface then extends to include the CH2OH-6 group of the αDGal unit intramolecularly hydrogen bonded to the O-5 atom. The stability of the complex is attributed to nonpolar interaction of this surface within a hydrophobic cleft-like combining site which offers a polar grouping at its periphery for interaction with the key polar grouping of the trisaccharide. The solution conformer for 1, as determined by 1H nmr, is present in its crystal structure.