Systematic synthesis and MAG-binding activity of novel sulfated GM1b analogues as mimics of Chol-1 (α-series) gangliosides: highly active ligands for neural siglecs ☆

Abstract Systematic synthesis and myelin-associated glycoprotein (MAG)-binding activity of novel sulfated GM1b analogues structurally related to Chol-1 (α-series) gangliosides, high-affinity ligands for neural siglecs, are described. The suitably protected gangliotriose derivatives, 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6- O -levulinoyl-β- d -galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β- d -galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β- d -glucopyranoside and 2-(trimethylsilyl)ethyl 2-acetamido-2-deoxy-6- O -levulinoyl-β- d -galactopyranosyl-(1→4)-2,6-di- O -benzyl-3- O -levulinoyl-β- d -galactopyranosyl-(1→4)-2,3,6-tri- O -benzyl-β- d -glucopyranoside were each glycosylated with α-NeuAc-(2→3)-galactose donor to give the corresponding pentasaccharides in 94% (β1,3 glycoside only) and 90% (β1,3:β1,4=2:1), respectively. After proper manipulation of the protecting groups, the pentasaccharides were converted into three novel sulfated GM1b gangliosides by the successive introduction of the ceramide and sulfo groups, followed by complete deprotection. Among the synthetic gangliosides, GSC-338 (II 3 III 6 -disulfate of iso -GM1b) was surprisingly found to be the most potent MAG binding structure tested to date.