title: The synthesis of deoxy-alpha-Gal epitope derivatives for the evaluation of an anti-alpha-Gal antibody binding.
abstract: Alpha-Gal epitopes (also termed as alpha-Gal) are carbohydrate structures bearing the alpha-D-Gal-(1-->3)-beta-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 alpha-Gal were synthesized. Inhibition ELISA using mouse laminin was established to determine the binding affinity of the synthesized alpha-Gal derivatives. 4-Deoxy-alpha-Gal derivative 7 showed a significant reduction in antibody recognition. The IC(50) value was 15-fold poorer than the standard alpha-Gal epitopes alpha-D-Gal-(1-->3)-beta-D-Gal-(1-->4)-beta-D-Glc-NHAc (39) and alpha-D-Gal-(1-->3)-beta-D-Gal-(1-->4)-beta-D-Glc-OBn (40). A similar observation was seen with 2-deoxy-alpha-Gal derivative 5, whose IC(50) 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-alpha-Gal derivative 8 exhibited similar antibody recognition to both alpha-Gal epitope 39 and alpha-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 alpha-Gal derivatives.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Janczuk
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Peter R
authors.initials: PR
authors.lastname: Andreana
authors.forename: Joshua
authors.initials: J
authors.lastname: Warrick
authors.forename: Peng G
authors.initials: PG
authors.lastname: Wang
mesh_terms: D000906:Antibodies; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D000939:Epitopes / Q000276:immunology; D005643:Fucose / Q000138:chemical synthesis* / Q000276:immunology*; D005690:Galactose; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000906:Antibodies; D004187:Disaccharides; D000939:Epitopes; D009844:Oligosaccharides; D005643:Fucose; D005690:Galactose