The synthesis of deoxy-α-Gal epitope derivatives for the evaluation of an anti-α-Gal antibody binding Original Research Article

α-Gal epitopes (also termed as α-Gal) are carbohydrate structures bearing the α-d-Gal-(1→3)-β-d-Gal terminus 1 and are known to be the antigen responsible for antibody-mediated hyperacute rejection in xenotransplantation. Terminal 2-, 3-, 4-, and 6-deoxy-Gal derivatives of α-Gal were synthesized. Inhibition ELISA using mouse laminin was established to determine the binding affinity of the synthesized α-Gal derivatives. 4-Deoxy-α-Gal derivative 7 showed a significant reduction in antibody recognition. The IC50 value was 15-fold poorer than the standard α-Gal epitopes α-d-Gal-(1→3)-β-d-Gal-(1→4)-β-d-Glc-NHAc (39) and α-d-Gal-(1→3)-β-d-Gal-(1→4)-β-d-Glc-OBn (40). A similar observation was seen with 2-deoxy-α-Gal derivative 5, whose IC50 value was nearly tenfold higher than the standards. Interestingly, substitution at the terminal 3-position resulted in only a fourfold decrease in antibody recognition, suggesting a possible point of future derivation. Finally, 6-deoxy-α-Gal derivative 8 exhibited similar antibody recognition to both α-Gal epitope 39 and α-Gal epitope 40. This strongly suggests that derivatization at the 6-position can be accomplished without loss of antibody recognition. These findings can be utilized for the future design of other α-Gal derivatives.