title: Conformational analysis of an alpha-galactosyl trisaccharide epitope involved in hyperacute rejection upon xenotransplantation.
abstract: alpha-Galactosyl epitopes are carbohydrate structures bearing an alpha-Gal-(1-->3)-Gal terminus (alpha-Gal epitopes). The interaction of these epitopes on the surface of animal cells with anti alpha-Gal antibodies in human serum is believed to be the main cause in antibody-mediated hyperacute rejection in xenotransplantation. In this paper, conformational analysis of an N-linked alpha-D-Galp-(1-->3)-beta-D-Galp-(1-->4)-beta-D-Glcp trisaccharide epitope was conducted in terms of each monosaccharide residue conformation, primary hydroxymethyl group configuration, and interglycosidic conformations. Selective 2D J-delta INEPT experiments have been carried out at three different temperatures to evaluate three-bond, long-range 13C-1H coupling constants for the crucial alpha-(1-->3) linkage. The NMR experimental data were complemented by theoretical calculations. The flexibility and dynamics of the trisaccharide have been studied by Metropolis Monte Carlo simulations. Ensemble-averaged three-bond, long-range 13C-1H coupling constants and nuclear Overhauser effects were in good agreement with the experimental data. The alpha-(1-->3) glycosidic linkage has shown a restricted flexibility as indicated by NMR spectroscopy and molecular modeling.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: M B
authors.initials: MB
authors.lastname: Ksebati
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Fang
authors.forename: P G
authors.initials: PG
authors.lastname: Wang
mesh_terms: D005690:Galactose / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D013816:Thermodynamics; D014183:Transplantation, Heterologous; D014312:Trisaccharides / Q000737:chemistry*
chemical_list: D014312:Trisaccharides; D005690:Galactose