Synthesis of ganglioside lactams corresponding to GM1-, GM2-, GM3-, and GM4-ganglioside lactones

Article abstract of DOI:10.1021/ja00122a002

Ganglioside lactams are potentially useful analogs of ganglioside lactones, which are highly immunogenic derivatives of gangliosides. The lactam corresponding to the G_M3-lactone saccharide has been synthesized by sialylation of a suitably protected lactose derivative carrying an azido group in the 2′-position, followed by reduction and ring closure to form G_M3-lactam. Glycosylation in the 4-position of the central saccharide unit gave the G_M2- and G_M1-lactam saccharides. By a similar route, a 2-azido-Gal derivative was sialylated and treated as above to give the G_M4-lactam saccharide. Deprotection gave the G_M2-₄-lactam saccharides in water soluble form, whereas attempted deprotection of the G_M1-lactam caused its degradation. The G_M3-lactam saccharide was coupled to ceramide, to afford the ganglioside lactam analog, and via a spacer to bovine serum albumin (BSA). The BSA conjugate was used as immunogen to raise monoclonal antibodies that cross-reacted with G_M3-lactone. The antibodies were used in a histological staining of murine melanoma cells, clearly showing the presence of G_M3-lactone on the cell surface. Keeping the G_M2-4-lactam saccharides in D₂O at 37 °C for 1 month caused marginal (0-11%) hydrolysis of the lactam ring.