Synthesis of complex carbohydrate antigens of pathogenic bacteria

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During the last few decades, increasing research in glycobiology has led to the identification of carbohydrates that play important key roles in cell signaling and immunology. Capsular polysaccharides (CPS) and/or lipopolysaccharides (LPS) are the major components on the surface of bacteria. Several higher monosaccharides (monosaccharides containing between 8 and 11 consecutive carbon atoms) have been isolated from bacterial CPS or LPS, and the synthesis of these carbohydrates could allow access to valuable potential antigenic molecules. The medically relevant 2-keto-ulosonic acid family have various biological functions and are constituents of bacterial CPS and/or LPS. Despite extensive efforts over the years, there is no general and practical route to the synthesis of these carbohydrates. The unifying theme of our research program is to exploit, through collaborative research, complex carbohydrates as new bactericidal molecules or galectin inhibitors. To reach this goal, we propose the evaluation of green chemistry towards a new synthesis of higher monosaccharides. To this end, a new de novo approach will give access to functionalized dihydropyrans via cascade reactions. Then, sialic acid will be polymerized and conjugated onto a new carrier protein (PaPMV coated protein) to achieve carbohydrate-based antibacterial vaccines. The discovery of new protein carriers in glycoconjugate vaccines is of great interest to the scientific community. Similarly, the synthesis of novel salic acid-based galectin inhibitors will allow a better understanding of the carbohydrates-protein interactions at the molecular level, leading to potential new drug design. These projects will contribute to the training of highly qualified scientists whose skills will benefit private and public research laboratories. The research program proposed will educate and train undergraduate and graduate students in the art and science of chemical synthesis in carbohydrate chemistry.