Chemical approaches to glycobiology and emerging carbohydrate-based therapeutic agents

The contributions of cell surface oligosaccharides to critical biological processes such as leukocyte-endothelial cell adhesion, bacterial and viral infection, and immunological recognition of tumor cells and foreign tissue are now understood in significant molecular detail. These discoveries at the forefront of biological research have motivated the design of synthetic glycoconjugates as tools for the fundamental study of glycobiology and as candidates for future generations of therapeutic and pharmaceutical reagents. During the past two years, significant progress has been made in the design and synthesis of carbohydrate-based inhibitors of selectins, receptors involved in the attachment of leukocytes to endothelial cells at sites of inflammation. Monomeric and multivalent oligosaccharides that bind to bacterial and viral receptors have been shown to abrogate infection by agents such as Helicobacter pilori, influenza virus and HIV. The identification of certain cell surface oligosaccharides as potent antigens has prompted their use in tumor vaccines, and inspired new approaches to the management of tissue rejection subsequent to xenotransplantation. To better understand how cell surface oligosaccharides function within their native context, novel chemical approaches to modulating cell surface oligosaccharide structures are now being developed. These stratergies for cell surface 'glycoform remodeling' promise to facilitate the investigation of carbohydrate-mediated cell-cell interactions.