Autor(es)Fujikawa Kohki,Nakashima Shinya,Konishi Miku,Fuse Tomoaki,Komura Naoko,Ando Takayuki,Ando Hiromune,Yuki Nobuhiro,Ishida Hideharu,Kiso Makoto

ResumoThe 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.

Palavras-ChaveGangliosides; Guillain-Barre syndrome; Natural products; Sialic acids; Total synthesis

ImprentaChemistry (Weinheim an der Bergstrasse, Germany), v. 17, n. 20, p. 5641-5651, 2011

DescritoresGuillain-Barre Syndrome - Molecular Structure ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Immunology

Data de Publicação:2011