研究领域

organic

Our research interests are in the area of bioorganic chemistry. The main objective is to develop and apply modern synthetic carbohydrate chemistry and bioorganic chemistry to the understanding of carbohydrate-protein interactions involved in tumorigenesis, cancer metastasis and infection, and to the design, synthesis and immunological evaluation of microbial and tumor-associated mammalian carbohydrate antigens. Our research adopts a multidisciplinary approach by engaging modern carbohydrate chemistry, biochemistry and immunochemistry by making use of novel knowledge acquired from biology’s newest discoveries to guide the design and synthesis of inhibitor molecules capable of selectively interfering with the crucial biosynthetic pathways that cancer cells rely on to survive, spread and proliferate and to raise antibodies with high immunospecificity and immunoaffinity to prevent infectious disease. Currently, our research is focused on the following four areas: (1). Rational design and synthesis of inhibitors for tumor-associated glycosyltransferases Glycosyltransferases are the primary gene products responsible for the biosynthesis of complex carbohydrates in living cells. Many human diseases are associated with abnormal glycosyltransferase activities which can lead to the over-expression or under-expression of carbohydrate structures. Since carbohydrates are the primary mediator molecules involved in all sorts of bio-recognition events, this can directly lead to the unusual behavior and biological functions of cells. With the help of computer modeling, we are actively involved in the design, synthesis and biological assaying of inhibitors for tumor-associated glycosyltransferases. (2). Synthesis and immunological evaluation of neoglycoconjugates for the prevention of infectious diseases and cancer The cell surface of many bacterial species is covered with polysaccharides. These extracellular carbohydrates can be in the form of glycolipids, glycoproteins or capsules. The capsular polysaccharides exist in both Gram-negative and Gram-negative bacteria such as Neisseria meningitidis, Haemophilus influenzae, E. coli, Streptococci pneumoniae etc. A special form of glycolipids is called lipopolysaccharides which exist only in Gram-negative bacteria. These polysaccharides are strain-specific and serve as virulence factors for the bacteria. Immune response against the cell surface polysaccharides can stimulate the hosts to produce strain-specific antibodies which can protect the hosts from future infections by the same bacterial strain. We are heavily involved in the synthesis and immunological evaluation of neoglycoconjugates related to some of the polysaccharides. (3). The development of clustering methodologies to synthesize conjugate vaccines with enhanced immunogenicity The surface of an immune B-lymphocyte is coated with thousands of receptors of single specificity. The binding and uptake of antigen molecules by B-cell receptors are crucial steps in humoral and cell-mediated immune responses. Clustering antigen molecules before presenting to B cells thus has the potential of increasing immunogenicity because this improves the binding to B-cell receptors through multivalent interactions. We are involved in developing efficient clustering methodologies to prepare conjugate vaccines with improved immunogenicity. (4). Conformational analysis and molecular modeling of carbohydrates The use of computer-aided conformational analysis and molecular modeling is an integrated part of our research. We rely on computers to help us to visualize and understand the molecular interactions involved in carbohydrate-protein recognitions and use the information to guide our design and synthesis of analogs with improved properties. We also carry out calculations in order to determine the conformation of carbohydrates and their analogs and correlate with crystallographic and NMR studies.

近期论文

查看导师最新文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Efficient synthesis of D-xylo and D-ribo-phytosphingosines and their unsaturated analogs. Y. Cai, C.-C. Ling and D. R. Bundle, Carbohydr. Res., 344, 2120-2126 (2009). Concise and Efficient Synthesis of 2-Acetamido-2-deoxy-β-d-hexopyranosides of Diverse Aminosugars from 2-Acetamido-2-deoxy-β-d-glucose. Y. Cai, C.-C. Ling and D. R. Bundle, J. Org. Chem., 74, 580-589 (2009). Reducing Epitope Spread during Affinity Maturation of an Anti-ganglioside GD2 Antibody. J. Hu, X. Huang, C.-C. Ling, D. R. Bundle and N.-K. V. Cheung, J. Immunol., 183, 5748-5755 (2009). Epitope Specificities of the Groups Y and W-135 Polysaccharides of Neisseria meningitides. S. L. Moore, C. Uitz, C.-C. Ling, D. R. Bundle, P. C. Fusco, and F. Michon, Clin. Vaccine Immunol., 14, 1311-1317 (2007). Sulfatide binding properties of murine and human antiganglioside antibodies. K. Townson, K. N Greenshields, J. Veitch, D. Nicholl, M. Eckhardt, O. Galanina, N. Bovin, E. Samain, T. Antoine, D. Bundle, P. Zhang, C.-C. Ling and H. J. Willison, Glycobiology, 17, 1156 - 1166 (2007). A general, efficient and stereospecific route to synthesize sphingosine, sphinganines and phytosphingosines and their analogs. Y. Cai, C.-C. Ling and D. R. Bundle, Org. Biomol. Chem., 4, 1140-1146 (2006). Chemoenzymatic synthesis of GM3 and GM2 gangliosides containing a truncated ceramide functionalized for glycoconjugation and solid phase applications. S. Jacques, J. R. Rich, C.-C. Ling and D. R. Bundle, Org. Biomol. Chem., 4, 142-154 (2006). Thio-oligosaccharide conjugate vaccines evoke antibodies specific for native antigens. D. R. Bundle, J. R. Rich, S. Jacques, H. N. Yu, M. Nitz and C.-C. Ling, Angew. Chem. Int. Ed., 44, 7725-7729 (2005). Facile approach to 2-acetamido-2-deoxy-D-glucopyranosides via a furanosyl oxazoline. Y. Cai, C.-C. Ling and D. R. Bundle, Org. Lett., 7, 4021-4024 (2005). A new homo-bifunctional para-nitro phenyl ester based coupling reagent for the preparation of neoglycoproteins. X. Wu, C.-C. Ling and D. R. Bundle, Org. Lett., 6, 4407-4410 (2004). Synthesis of ganglioside epitopes for oligosaccharide specific immunoadsorption therapy of Guillian-Barré Syndrome. S. M. Andersen, C.-C. Ling, P. Zhang, K. Townson, H. J. Willison and D. R. Bundle, Org. Biomol. Chem., 2, 1199-212 (2004). Synthetic disialylgalactose immunoadsorbents deplete anti-GQ1b antibodies from autoimmune neuropathy sera. H. J. Willison, K. Townson, J. Veitch, J. Boffey, N. Isaacs, S. M. Andersen, P. Zhang, C.-C. Ling and D. R. Bundle, Brain, 127, 680-691 (2004). Synthesis of disaccharide congeners of the Trichinella spiralis glycan and binding site mapping of two protective antibodies. P. Zhang, J. A. Appleton, C.-C. Ling and D. R. Bundle, Can. J. Chem., 80, 1141-1161, (2002). Probing carbohydrate-antibody interactions: synthesis of three salmonella epitopes for SPR studies. H. N. Yu, C.-C. Ling and D. R. Bundle, Can. J. Chem., 80, 1131-1140 (2002). The unique solution structure and immunochemistry of the Candida albicansb-1,2-mannopyranan cell wall antigens. M. Nitz, C.-C. Ling, A. Otter, J. E. Cutler and D. R. Bundle, J. Biol. Chem., 277: 3440-3446 (2002). The syntheses of 6-C-alkyl derivatives of methyl a-isomaltoside for a study of the mechanism of hydrolysis by amyloglucosidase. U. Spohr, N. Le, C.-C. Ling and R. U. Lemieux, Can. J. Chem., 79, 238-255 (2001). Efficient stereoselective synthesis of 1-thio-b-mannopyranosides. H. N. Yu, C.-C. Ling and D. R. Bundle, J. Chem. Soc. Perkin Trans. I, 832-837 (2001). A tethered disaccharide trapped as its anti conformer calibrates the karplus relationship for 3JC-H coupling constants. S. A. Wacowich-Sgarbi, C.-C.Ling, A. Otter and D. R. Bundle, J. Am. Chem. Soc., 123, 4362-4363 (2001). The epitope of the H-type 2 trisaccharide recognized by Erythrina corallodendron lectin. Evidence for both attractive polar and strong hydrophobic interactions for complex formation involving a lectin. R. U. Lemieux, C.-C. Ling, N. Sharon and H. Streicher, Israel J. Chem., 40, 167-176 (2000). A practical route to 3,6-dideoxyhexoses. H. N. Yu, P. Zhang, C.-C. Ling and D. R. Bundle, Tetrahedron Asymmetry, 11, 465-479 (2000).