| In recent years, complex carbohydrates and glycopeptides have been shown to play central roles in many important biological events, such as inflammation, infection, metastasis, and the immune response. Therefore the synthesis of glycopeptides and similar compounds has become an area of considerable interest in the attempt to develop therapeutic uses for carbohydrates. One particular area of interest that has received a great attention is the development of carbohydrate based cancer vaccines. Current vaccine candidates are based on the fusion of various glycosides to immunogenic peptides through N- or O-linkages. These bonds, however, have proven to be labile under normal biological conditions in the body. It was envisioned that the use of carbon-linked glycopeptides would result in more stable conjugates without a large difference in biological function. In order to test this hypothesis, methods were developed to obtain various C-linked glycoamino acids and glycopeptides through the use of olefin metathesis. Studies were also completed on the synthesis of many new alpha and beta-C-glycosides, including C-analogs of known tumor associated cancer antigens. Research also focused on the development of post- and co-translational methods of glycopeptide synthesis, with attempts to expand solid phase synthesis for the optimization of glycosylation. |
