Synthesis and Applications of Biologically Active Carbohydrate Derivatives and Related Compounds

这份提案包含三个独立的部分。第一部分建议改进针对尿路感染(UTI)的防粘连策略，UTI是第二种最常见的疾病。抗粘连药物干扰细菌蛋白质与组织表面碳水化合物的结合，从而防止细菌定植。持续性尿路感染是由某些菌株表面丝状突起末端的一种蛋白质FimH与尿路表面的一种蛋白质Uroplakin Ia上的甘露糖结合而起的。结合改变了构成细菌表面的分子的形状，使细菌得以进入和定居。我们的建议是合成与已知的最好结合甘露糖衍生物的结构相匹配的化合物，然后尽可能多地将其附着到聚酯树枝状大分子或树枝状纳米颗粒或树枝状聚合物上，以结合每个细菌上尽可能多的200-500菌毛，以消除被屏蔽的细菌菌落。

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.