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

我们研究小组的基本专业知识在于合成碳水化合物化学。最近，我们已经建立了更多的专业知识，在分子建模的寡糖使用的分子力学方法和NMR测量相结合。 我们主要研究项目的主要目标是通过化学合成设计基于肿瘤相关碳水化合物（TAC）二聚LeX和LeALEX的安全抗癌疫苗。 使用这些TAC作为破坏肿瘤细胞的靶点受到以下事实的阻碍，即这些大结构的片段莱亚和LeX三联体在许多正常细胞的表面表达。 因此，当使用靶向二聚LeX和LeALEX的抗癌药物或疫苗时，正常细胞有被破坏的风险。 在这种情况下，我们的研究旨在发现这些大六糖的类似物和片段，它们不再显示LeX或莱亚三糖，但仍然可以触发免疫应答，识别肿瘤细胞上表达的TAC。我们还建立了第二个研究领域，旨在设计和制备可以通过糖残基携带的硫醇固定在金上的假糖脂。这些分子将用于通过将脂质部分插入双层的第一小叶来将双层脂质膜拴系在金表面上。由于碳水化合物，然后将提供锚定的双层和金表面之间的水层，这些结构应该允许使用现代国家的最先进的分析技术，如电化学扫描隧道显微镜（EC-STM）和原子力光谱（AFM）的生物跨膜事件的研究。

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).