title: The first total synthesis of ganglioside GalNAc-GD1a, a target molecule for autoantibodies in Guillain-Barré syndrome.
abstract: The first synthesis of ganglioside GalNAc-GD1a, featuring efficient glycan assembly and a cyclic glucosyl ceramide as a versatile unit for ganglioside synthesis is described. Although ganglioside GalNAc-GD1a was first found as a brain ganglioside, IgG autoantibodies to GalNAc-GD1a were subsequently found to be closely related to a human peripheral-nerve disorder, Guillain-Barré syndrome, which is the commonest cause of acute flaccid paralysis worldwide. In this study, the characteristic hexasaccharide part carrying two sialic acid residues was synthesized efficiently by use of a readily accessible GM2-core unit as a common unit. The potentially difficult coupling of the oligosaccharide and ceramide moieties was carried out by using a cyclic glucosyl ceramide as a coupling partner for the hexasaccharide part, thereby successfully providing the framework of the target compound. Global deprotection delivered the homogenous ganglioside GalNAc-GD1a. An enzyme-linked immunosorbent assay showed that sera from patients with Guillain-Barré syndrome reacted both with natural and with synthetic GalNAc-GD1a.
authors.affiliation: Department of Applied Bioorganic Chemistry, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan.
authors.forename: Kohki
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Nakashima
authors.forename: Miku
authors.initials: M
authors.lastname: Konishi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fuse
authors.forename: Naoko
authors.initials: N
authors.lastname: Komura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ando
authors.forename: Hiromune
authors.initials: H
authors.lastname: Ando
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yuki
authors.forename: Hideharu
authors.initials: H
authors.lastname: Ishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D005732:Gangliosides / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D005732:Gangliosides; D012794:Sialic Acids; C055253:IV(4)-galactosyl-N-acetylganglioside GD1a