Carbohydrates are widely distributed as glycoproteins or glycolipids on mammalian cell surface. Most of these carbohydrate moieties have sialic acid residues as the terminal units. Despite their important roles, carbohydrates in glycoproteins usually do not occupy or block the protein critical active sites. Therefore, carbohydrates, especially the terminal sialic acid residues, are ideal sites for modification and conjugation.
Anti-cancer monoclonal antibodies have widely applications in both experimental and clinical studies. Recently developed humanized monoclonal antibodies found great potential in anticancer therapy. Both human and mouse immunoglobulin IgG1 antibodies contains two heavy chains. There is an asparagine-linked (N-linked) oligosaccharide on the CH2 domain of each heavy chain. These N-linked oligosaccharides are generally restricted to biantennary oligosaccharides terminating in 2, 1, and 0 galactose residues. Using a beta-1,4-galactosyltransferase and a sialyltransferase, functional group-tagged sialic acid can be enzymatically conjugated to anticancer monoclonal antibodies. These functional groups-tagged antibodies can be applied in anticancer pretargeting as attractive delivery vehicles for radionuclides, drugs, toxins, and 10B-enriched carboranes to tumors.