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

寡糖和糖复合物的合成：寻找新型抗癌疫苗并设计新型系链分子以将双层脂膜锚定到金上

• 批准号: 238355-2011
• 负责人: Auzanneau, FranceIsabelle
• 金额: $ 3.28万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570404
• 关键词: Synthesis; oligosaccharides; glycoconjugates; search; novel

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).

我们研究小组的基本专长是合成碳水化合物化学。最近，我们在使用分子力学方法和核磁共振测量相结合的低聚糖分子建模方面建立了额外的专业知识。