Progress towards the development of fully synthetic carbohydrate-based cancer vaccines

Research on the synthesis of glycoproteins has received considerable attention over the past years due to their importance in numerous disease states. The carbohydrate subunits of these glycoproteins play a central role in various key biological events including immune response, inflammation, metastasis, and infection. Consequently, great emphasis has been placed on the development of effective therapeutic strategies based upon recognition of these cell surface carbohydrate moieties. The progress of carbohydrate-based therapeutic agents has been hampered by the lability of the N- or O-linkages between the carbohydrate residue and the peptide backbone. An attractive solution to this biological instability is the replacement of the N- or O-linkages with C-linkages that are more resistant to enzymatic degradation. With this in mind, we envision that C-analogues of known tumor-associated cancer antigens may exhibit greater biological activity than the naturally occurring residues. To test our theory, it was necessary to develop methodology that would lead to a range of stereoisomeric C-analogues of known tumor-associated cancer antigens and would allow for their coupling to peptide fragments. With this in mind, the present studies address the development of methodology towards the design and chemical synthesis of fully synthetic vaccines for the treatment, and perhaps prevention, of cancer.