Synthesis of 3-aminopropyl β-glycoside of sialyl-3′-lactose and derived neoglycoconjugates as a tumor vaccine prototype and artificial antigens for the control of immune response

Starting from the biotechnologically available trisaccharide sialyl-3′-lactose, representing the carbohydrate portion of the tumor-associated ganglioside GM3, the corresponding 3-aminopropyl β-glycoside (1) and 3-(4-maleimidobutanoylamino)propyl glycoside were synthesized. The reaction of the latter with a thiolated derivative of the Megathura crenulata hemocyanine (KLH) afforded a carbohydrate—protein conjugate, a tumor vaccine prototype containing about 330 trisaccharide ligands attached to KLH. N-Stearoylation of ligand 1 gave the model neoglycolipid for comparative study of the activity of mono-and polyvalent immunogens and the natural ganglioside GM3. A monovalent conjugate, in which ligand 1 is linked to biotin through an oligo(ethylene glycol) spacer and a polyvalent conjugate with a polyacrylamide carrier were also prepared. These conjugates are meant as covering antigens to assess the specificity and efficiency of the immune response in the ELISA assay.