ANALYSIS AND SYNTHESIS OF CARBOHYDRATE ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS

结核分枝杆菌碳水化合物抗原的分析与合成

• 批准号: 6162487
• 负责人: V POZSGAY
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162487
• 关键词: Mycobacterium tuberculosis; bacterial antigens; bacterial polysaccharides; chemical structure function; chemical synthesis; human tissue

Mycobacterium tuberculosis, the causative organism of tuberculosis is responsible for approximately three million death cases annually and the mortality rate of infections caused by multiple drug-resistant strains of this bacterium exceeds 80%. M. tuberculosis is coated by a number of polysaccharides of unusual structure. A unique component termed polysaccharide II is said to be composed of alpha 1,2-linked D-glucose residues. Schemes were designed to isolate this polysaccharide from polysaccharide-containing extracts of M. tuberculosis. In search for this putative antigen we chemically synthesized oligosaccharides correponding to polysaccharide II and developed methods for their covalent attachment to proteins to render them immunogenic, in a controlled manner. We demonstrated that the major monosaccharide components in soluble polysaccharide fractions from Mycobacteria are glucose, arabinose, mannose and galactose. A number of polysaccharide fractions were analyzed and some were found to contain mainly or exclusively d-glucose. Nuclear magnetic resonance spectra indicate that the glucose-containing polysaccharide fractions have the same overall structure as the glycogen-like polysaccharide isolated from M. tuberculosis many years ago by Siebert. None of the polysaccharide fractions appeared to be identical to the putative polysaccharide II.

结核分枝杆菌是结核病的病原体， 每年造成大约300万例死亡， 多重耐药菌株感染的死亡率 这种细菌超过80%。 M.结核病被许多 不寻常结构的多糖。 一种独特的成分， 多糖II据说由α 1，2-连接的D-葡萄糖组成 残基 设计方案以分离该多糖， 含多糖的M.结核 在寻找 我们化学合成了这种推定的抗原低聚糖 对应于多糖II，并开发了其制备方法。 共价连接到蛋白质上，使其具有免疫原性， 控制的方式。 我们证明了主要的单糖 来自分枝杆菌的可溶性多糖级分中的组分是 葡萄糖、阿拉伯糖、甘露糖和半乳糖。 一些多糖 馏分进行了分析，发现一些主要含有或 仅D-葡萄糖。 核磁共振谱表明， 含葡萄糖的多糖级分具有相同的总体 结构与从M. 结核病多年前由Siebert。 没有一种多糖 级分似乎与推定的多糖II相同。