Faculty Research
Alphabetical · By research area

Research interests are centred on protein-carbohydrate interactions with particular emphasis on the relatively small carbohydrate recognition element (epitope) that contacts the protein binding site. Antibodies against microbial carbohydrate antigens afford protection against infection and protein oligosaccharide conjugate vaccines are one of the most successful public health measures against serious diseases. Other important protein carbohydrate interactions involve adherence of bacteria or their toxins to the mammalian cell surface oligosaccharides of glycolipids, and N-linked and O-linked glycoproteins.

The group currently focuses on two major themes: design, synthesis and evaluation of conjugate vaccines against bacterial and fungal diseases and the development of novel approaches for the design and synthesis of inhibitors to block bacterial toxin and virus binding to mammalian cells. The approach adopted is multidisciplinary and involves the synthesis of oligosaccharide epitopes generally consisting of 2-5 hexose residues, and NMR experiments to determine solution conformation in the free and bound states. Special emphasis is placed on the accurate determination of the thermodynamics of binding using sensitive techniques such as titration microcalorimetry. The structure activity relationships that emerge are used to guide the design and synthesis of inhibitors. Research on toxin inhibitors involves a large component of computational approaches and molecular modeling studies.

Our laboratory is part of the Alberta Glycomics Centre. Several of our projects involve national and international collaborations with crystallographers and bio-medical research groups. Current targets and practical applications of the research are synthesis of microbial antigens, glycolipid adjuvants, cancer associated glycosphingolipids, and the design and synthesis of high affinity inhibitors to block bacteria adherence or bacterial toxin binding to human cells. Examples of funded projects include:

• Novel approaches in the design of conjugate vaccines to combat microbial infections
• "Candida albicans Conjugate Vaccines: Evaluation of synthetic beta-mannan oligosaccharides conjugated to immunogenic carriers in rabbit and mouse models of experimental candidiasis."
• "Multivalence assisted supramolecular assembly in biological systems."

Selected Publications

Xin , H., Dziadek, S., Bundle, D. R. and Cutler, J. "Synthetic glycopeptide vaccines combining ß-mannan and peptide epitopes induce protection against candidiasis." Proc. Natl. Acad. Sci (USA) 2008, 105, 13526-13531..

Kitov, P. I., Mulvey, G. L., Griener, T., Lipinski, T., Solomon, D., Paszkiewicz, E., Jacobson, J. , Sadowska, J. M., Suzuki, M., Yamamura, K., Armstrong, G. D. and Bundle, D. R. "In vivo supramolecular templating enhances the activity of multivalent ligands: A potential therapeutic against the E. coli O157 AB5 toxins." Proc. Natl. Acad. Sci (USA) 2008, 105, 16837-16842.

Wu, X., Cui, L., Lipinski, T. and Bundle, D.R. "Synthesis of monomeric and dimeric repeating units of the zwitterionic type 1 capsular polysaccharide from Streptococcus pneumoniae." Chem. Eur. J. 2010, 16, 3476-3488.

Tran, H.-A., Kitov, P. I., Paszkiewicz, E., Sadowska, J. M. and Bundle, D. R. "Multifunctional multivalency: a focused library of polymeric cholera toxin antagonists." Org. Biomol. Chem. 2011, 9, 3658-3671.

Guiard, J., Langpap, B., Kitov, P., Peters, P. and Bundle, D. R. "'Double-Click' Protocol for Synthesis of Heterobifunctional Multivalent Ligands: Toward a Focused Library of Specific Norovirus Inhibitors." Chem. Eur. J. 2011, 17, 7438-7441.

Rademacher, C., Guiard, J., Kitov, P., Langpap, B., Dalton, K. P., Parra, F., Bundle, D. R. and Peters, P. "Targeting Norovirus Infection - Multivalent Entry Inhibitor based on NMR Data." Chem. Eur. J. 2011, 17, 7442-7453.