Synthesis of glycoconjugates to elicit carbohydrate-specific immune responses and enhance molecular recognitions

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Carbohydrates are ubiquitous and implicated in all cell-cell communications. Our research interests are to develop new methodologies and apply recent advances in carbohydrate chemistry, molecular biology and supramolecular chemistry to the design and synthesis of novel analogs related to bioactive carbohydrates as well as to the understanding of relevant biorecognition mechanisms. Two objectives are pursued: the first is to prepare carbohydrate-protein conjugates (vaccines) capable of stimulating hosts to generate long-lasting immune responses; the second objective is to design and synthesize carbohydrate based ligands for use as inhibitors capable of competitively binding to proteins such as enzymes, toxins, lectins, in order to block undesired recognitions. In the context of our first objective, our research can lead to the production of preventive vaccines against bacterial infections, or to the generation of therapeutic antibodies with potential to selectively eliminate malignant tumour cells. In the context of the second objective, if the undesired interaction is from an enzyme's recognitions of a substrate, our research can generate high affinity ligands capable of binding to the enzyme's active site, leading to a downregulation of enzyme's efficiency to produce undesired molecules; if the undesired interaction is directly linked to the attachment of pathogens, such toxins to carbohydrates present on the surface of host cells, our research could lead to the generation of high affinity carbohydrates based therapeutics capable of preventing the pathogenic attachment. Based on the concepts outlined above and on results obtained during past three years, we propose to conduct research in the following three areas: the first is related to the chemistry of alpha(2,8)-linked oligosialosides and their immunochemistry; the second is related to the development of synthetic methodology for KDO glycosides and the third is to investigate the potential of utilizing multi-substituted cyclodextrins as building blocks to generate novel cyclodextrin-based supramolecular systems capable of engaging protein binding sites across large distances.