Solution structure of two xenoantigens: αGal-LacNAc and αGal-Lewis X

• Published in: Glycobiology (Oxford) Vol. 12; no. 4; pp. 241 - 250
• Main Authors: Corzana, Francisco, Bettler, Emmanuel, Hervé du Penhoat, Catherine, Tyrtysh, Tatyana V., Bovin, Nicolai V., Imberty, Anne
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2002; Oxford University Press (OUP)
• Subjects: Antigens, Heterophile - chemistry; Biochemistry, Molecular Biology; Carbohydrate Conformation; Carbohydrate Sequence; Key words: /molecular dynamics/NMR/oligosaccharides/xenotransplantation; Life Sciences; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Oligosaccharides - chemistry; Solutions
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/12.4.241

Organ hyperacute rejection, a phenomenon occurring during discordant xenotransplantation, is due to the recognition of an oligosaccharide epitope by human xenoreactive natural antibodies. In addition to the αGal(1-3)βGal(1-4)GlcNAc trisaccharide, a fucosylated structure, αGal-Lewis X, has been shown to be recognized by the antibodies. Both the trisaccharide and the tetrasaccharide have been synthesized by chemical methods. A complete nuclear magnetic resonance characterization of the two compounds has been performed, including the measurements of two-dimensional nuclear Overhauser effect spectroscopy data. Molecular dynamics simulations were run for several ns in the presence of explicit water molecules. The combination of experimental and theoretical approaches revealed the effect of an additional fucose residue on the conformational behavior of the xenoantigen. This branched fucose strongly rigidifies the N-acetyllactosamine. The effect on the αGal(1-3)Gal fragment is less marked. In the presence of fucose, the terminal αGal residue can still adopt two different conformations, but the equilibrium populations are modified.