Synthesis and Applications of Biologically Active Carbohydrate Derivatives and Related Compounds

生物活性碳水化合物衍生物及相关化合物的合成及应用

• 批准号: 9912-2012
• 负责人: Grindley, Bruce
• 金额: $ 2.55万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=592982
• 关键词: Synthesis; Applications; Biologically; Active; Carbohydrate

This proposal contains three separate sections. The first section proposes improvement of the anti-adhesion strategy against urinary tract infections (UTI), the second most diagnosed disease. Anti-adhesion drugs interfere with the binding of bacterial proteins to carbohydrates on tissue surfaces and thereby prevent bacterial colonization. Persistant UTI are initiated by binding of a protein, FimH, at the end of threadlike projections from the surfaces of certain strains of E. coli, to mannose attached to one of the proteins, uroplakin Ia, at the surface of the urinary tract. Binding changes the shape of the molecules making up the surface that allows bacterial entry and colonization. The proposal is to synthesize compounds that match what is known about the structures of the best binding mannose derivatives, then attach as many as possible to polyester dendrimers or to dendritic nanoparticles or to dendritic polymers, so as to bind as many as possible of the 200-500 pili on each bacterium, to eliminate the shielded bacterial colonies.

这项建议包括三个独立的部分。第一部分提出了针对尿路感染（UTI）的抗粘连策略的改进，这是第二大诊断疾病。抗粘附药物干扰细菌蛋白与组织表面碳水化合物的结合，从而阻止细菌定植。持续性尿路感染是由一种蛋白质（FimH）与附着在尿路表面的一种蛋白质（uroplakin Ia）上的甘露糖结合而引发的，这种蛋白质位于某些大肠杆菌表面的线状凸起末端。结合改变了构成细菌进入和定植表面的分子的形状。建议是合成与已知的最佳结合甘露糖衍生物结构相匹配的化合物，然后将尽可能多的化合物附着在聚酯树状大分子或树状纳米颗粒或树状聚合物上，以便在每个细菌上结合尽可能多的200-500个菌毛，以消除被屏蔽的细菌菌落。