Synthesis of oligosaccharides and glycoconjugates: search for novel anti-cancer vaccines and design of novel tether molecules to anchor bilayer lipid membranes to gold

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The basic expertise of our research group resides in synthetic carbohydrate chemistry. More recently, we have established additional expertise in molecular modeling of oligosaccharides using a combination of molecular mechanics methods and NMR measurements. The main goal of our primary research program is to design through chemical synthesis safe anti-cancer vaccines based on Tumor Associated Carbohydrates (TACs) dimericLeX and LeALeX. Using these TACs as targets for the destruction of tumor cells is hampered by the fact that the LeA and LeX trisaccharides, which are fragments of these large structures, are expressed at the surface of many normal cells. Thus, when using anti-cancer drugs or vaccines that target dimericLeX and LeALeX, normal cells are at risk to be destroyed. In this context, our research aims at discovering analogues and fragments of these large hexasaccharides that no longer display the LeX or LeA trisaccharide but can still trigger an immune response that will recognize the TAC expressed on tumor cells. We have also established a second area of research that aims at designing and preparing pseudo-glycolipids that can be immobilized on gold via a thiol carried by the sugar residue. These molecules will be used to tether bilayer lipid membranes on a gold surface through the insertion of the lipid moiety into the first leaflet of the bilayer. Since the carbohydrate will then provide an aqueous layer between the anchored bilayer and the gold surface these constructs should permit the study of biological transmembrane events using modern state-of-the-art analytical techniques such as electrochemical scanning tunnelling microscopy (EC-STM) and atomic force spectroscopy (AFM).