绿脓杆菌O6血清型O-抗原四糖重复单元的全合成及其抗原性研究

绿脓杆菌是引起医院感染的主要病原体之一，不断形成的多重抗生素耐药性使得绿脓杆菌疫苗的开发迫在眉睫。脂多糖O-抗原已广泛应用于绿脓杆菌疫苗的研发，绿脓杆菌O6血清型O-抗原具有高度结构特异性，是绿脓杆菌糖类疫苗开发的重要靶点。本项目开展绿脓杆菌O6血清型脂多糖O-抗原四糖重复单元的全合成及其抗原性研究，基于氨基和羧基的正交保护、1,2-顺式-α-糖苷键的立体选择性合成和2-氨基半乳糖醛酸C4位羟基的反应活性调控等策略的发展来实现其化学全合成，并从糖链结构、糖链长度和修饰基团等方面出发制备包含O-抗原四糖及其衍生物的6种寡糖片段。利用绿脓杆菌抗血清，通过糖芯片技术分析寡糖片段库，研究O-抗原寡糖的抗原性及其构效关系。本项研究可为其它复杂高密度修饰氨基寡糖的全合成提供参考；从分子水平探究寡糖结构与其抗原性的关系，进而为绿脓杆菌糖疫苗的研发提供理论基础。

Pseudomonas aeruginosa has been one of the major pathogens responsible for a wide variety of nosocomial infections. Since the occurence of multiple antibiotic resistance, the development of vaccines against P. aeruginosa infection for humans has been an extremely urgent task. P. aeruginosa O6 serotype O-antigen has high structural specificity and has been identified as a potential antigen for the development of a glycoconjugate vaccine. This study focuses on chemical synthesis and antigenicity analysis of the P. aeruginosa serotype O6 O-antigen tetrasaccharide repeating unit. The orthogonal protection strategy for amino and carboxyl groups, stereoselective synthesis of 1,2-cis-α-glycoside and regulation of the reactivity of 2-aminogalacturonic acid C4 hydroxyl group will be involved in the chemical synthesis of P. aeruginosa serotype O6 O-antigen tetrasaccharide. An oligosaccharide antigen library containing O-antigen tetrasaccharide and its derivatives were prepared for exploring the detailed structure and immunological activity relationship. Glycan microarray analysis of sera of P. aeruginosa to investigate the antigenicity and structure-activity relationship of O-antigen oligosaccharides. This study will provide references for the total synthesis of other densely functionalized complex oligosaccharides. Exploring the relationship between the structure and their antigenicity at the molecular level to provide a theoretical basis for the development of P. aeruginosa glycoconjugate vaccines.