The molecular recognition of complex carbohydrates by proteins at the surfaces of mammalian cells and of microbes is the basis of their biological function. We utilize the power of chemical synthesis to create modified antigens that can reveal the structural basis of the recognition of carbohydrate antigens by antibodies and lectins. In turn our appreciation of the fine structure of numerous carbohydrate antigen-antibody complexes facilitates the design of conjugate vaccines for applications in cancer therapy and for prevention of serious microbial infections (Proc. Natl. Acad. Sci (USA), 105, 13526-13531, 2008).

Our group has had a long standing interest in the chemistry and glycobiology of complex carbohydrate antigens of bacterial and mammalian cells. Our earlier work included development of methods to synthesize and utilize neoglyconconjuagtes, for example in the creation of monoclonal antibodies with well-defined binding profiles. Subsequently these antibodies were the topic of interdisciplinary collaborations that resulted in the first crystal structures of an oligosaccharide-Fab complex and characterization of the energetics of the molecular recognition event by isothermal titration microcalorimetry. The group was also active in the application of NMR methods to primary antigen structure determination and to the determination of solution conformation in the free and bound state.
Since our group moved to the University of Alberta, we have continued to utilize and combine the tools of synthetic chemistry, biophysics and structural biology to address questions related to the intrinsically weak interactions that characterize sugar-protein interactions. We have combined three dimensional structural detail with studies of antibody-antigen interactions by physical methods including NMR and microcalorimetry, and we are using the well defined structural details of a variety of carbohydrate binding sites to pursue the rationale design of high affinity ligands. A recent success involved the design of a high avidity ligand for the Shiga like toxin responsible for the diseases that result from pathogenic E. coli O157 (Nature, 403, 669-672, 2000). This result was characterized by Professor Fraser Stoddart as "one of the most impressive applications of glycoscience to have been described in the literature to date" (Bioconjugate Chemistry, 12, 655-672, 2001). A second generation inhibitor based on heterobifunctional ligands protects mice against this toxin (Proc. Natl. Acad. Sci (USA), 105, 16837-16842, 2008).