The reducing end of αGal oligosaccharides contributes to their efficiency in blocking natural antibodies of human and baboon sera

Abstract

Abstract Synthetic galactosyl oligosaccharides were tested for their ability to inhibit the cytotoxic reaction of human and baboon natural antibodies on PK15 cells in culture. Methyl-α-Gal gave weak inhibition, Galal-3Gal substantially inhibited the reaction (400 µM), and Galα1-3Galβ 1-4GlcNAc was ten times more efficient (30 µM). The modification from a to β anomeric configuration of the nonreducing end resulted in a complete loss of activity, while substitutions at the reducing end induced only a partial loss of activity. These observations suggest that natural anti-αGal antibodies recognize the epitope from its non-reducing end, but that substitutions at the reducing terminus can modify the antibody-binding capacity. Modified tri- and tetrasaccharides are better inhibitors than the disaccha-ride but not as good as Galα1-3Galβ 1-4GlcNAc. The reducing terminus therefore contributes some energy to the reaction, indicating that certain oligosaccharides will be of more potential clinical use than others.