Synthetic tumor-associated glycopeptide antigens from the tandem repeat sequence of the epithelial mucin MUC4

In cancer research, the development of vaccines against tumor-associated antigens is of particular interest. Epithelia] cells express mucin type glycoproteins, which are extensively O-glycosylated. In case of cancer, the expression of these mucins is increased, and their carbohydrate side chains show an aberrant glycosylation pattern. A set of single and double glycosylated bexadecapeptides representing the tandem repeat sequence of the epithelial mucin MUC4 carrying different tumor-associated carbohydrate antigens was prepared by sequential solid-phase glycopeptide synthesis. The crucial glycosyl amino acid building blocks containing the T-N, T, sialyl-T-N and (2,6)-sialyl-T antigens were synthesized according to a biomimetic strategy by stepwise extension of the saccharide side chain of a Fmoc-protected galactosamine threonine tert-butyl ester precursor.