CHEMICAL APPROACHES TO GLYCOBIOLOGY AND EMERGING CARBOHYDRATE-BASED THERAPEUTIC AGENTS

The contributions of cell surface oligosaccharides to critical biologi cal processes such as leukocyte-endothelial cell adhesion, bacterial a nd viral infection, and immunological recognition of tumor cells and f oreign tissue are now understood in significant molecular detail. Thes e discoveries at the forefront of biological research have motivated t he design of synthetic glycoconjugates as tools for the fundamental st udy of glycobiology and as candidates for future generations of therap eutic and pharmaceutical reagents. During the past two years, signific ant progress has been made in the design and synthesis of carbohydrate -based inhibitors of selectins, receptors involved in the attachment o f leukocytes to endothelial cells at sites of inflammation. Monomeric and multivalent oligosaccharides that bind to bacterial and viral rece ptors have been shown to abrogate infection by agents such as Helicoba cter pilori, influenza virus and HIV. The identification of certain ce ll surface oligosaccharides as potent antigens has prompted their use in tumor vaccines, and inspired new approaches to the management of ti ssue rejection subsequent to xenotransplantation. To better understand how cell surface oligosaccharides function within their native contex t, novel chemical approaches to modulating cell surface oligosaccharid e structures are now being developed. These stratergies for cell surfa ce 'glycoform remodeling' promise to facilitate the investigation of c arbohydrate-mediated cell-cell interactions.