Structure analysis of the major oligosaccharides accumulating in canine GM1 gangliosidosis liver.

A homologous series of structurally related, high molecular weight oligosaccharides have been isolated and purified from the livers of a mixed breed of Beagle dogs affected with GM1 gangliosidosis. Five individual oligosaccharide fractions were purified by charcoal chromatography, preparative silicic acid thin layer chromatography, and gel filtration chromatography. Molecular size determinations revealed that these oligosaccharides contained 6, 9, 11, and 13 sugar residues, respectively. Detailed structure analysis was carried out on the most abundant fractions, oligosaccharides 1,2 and 3 (OS 1,2 and OS 3) using permethylation analysis and 360-MHz proton magnetic resonance spectroscopy coupled with sequential exoglycosidase degradation. OS 1,2 was a mixture of two linear isomeric hexasaccharides and OS 3 was a nonasaccharide containing a bianntenary branched mannosyl core. The proposed structures are: (formula see text) These compounds are nearly identical with the oligosaccharides stored in human GM1 gangliosidosis liver but they differ from the human compounds uniquely since they contain 2 GlcNAc residues at the reducing terminus instead of 1, suggesting that there may be significant differences in glycoprotein metabolism or structure between mammalian species.