STRUCTURE AND IMMUNOCHEMISTRY OF CAPSULAR POLYSACCHARIDES

荚膜多糖的结构和免疫化学

• 批准号: 3804609
• 负责人: W F VANN
• 金额: --
• 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/3804609
• 关键词: Neisseria meningitidis; bacterial capsules; bacterial polysaccharides; carbohydrate structure; chemical structure function; chemical synthesis; immunochemistry; immunoconjugates; nuclear magnetic resonance spectroscopy; oligosaccharides

This project developed from the project on the structure and immunochemistry of Staphylococcal polysaccharides. The objectives are several fold (a) investigate and develop methodology for structural analysis of capsular polysaccharides of pathogenic bacteria (b) development approaches for the synthesis of polysaccharide protein conjugates containing repeating structures of polysaccharides associated with pathogenic bacteria. In collaboration with Dr. R.A. Byrd of Division of Biochemistry and Biophysics, uniformly labeled 13C labeled K15 polysaccharide was prepared. This polysaccharide was used to develop 3-dimensional NMR techniques useful for the structural analysis of polysaccharides. In order to prepare a conjugate vaccine to Neisseria meningitidis Group A and to investigate the role of oligosaccharide structure and size on immunogenicity and approached was devised to chemically synthesize the repeating oligosaccharide. The first stage of the project involves the synthesis of a suitably protected and activated saccharide monomer. The following groups have been successfully introduced into N-acetylmannosamine 1-p-methoxybenzyl, 3-O-acetyl, 4-benzyl, 6-fluorenecarboxyl. In addition, the 1-protecting group has been selectively removed. The final step is the addition of a phosphoramidite group at the 1-position. In the next period a suitable linker arm will be attached to controlled pore glass and monomers will be constructed on the support.

这个项目是从结构上的项目发展而来的 葡萄球菌多糖的免疫化学。目标是 几个方面(A)研究和开发结构的方法 病原菌荚膜多糖的分析(二)发育 多糖类蛋白质结合物的合成方法 含有与以下物质相关的多糖的重复结构 病原菌。 与生物化学部R.A.伯德博士合作 生物物理学，制备了均一标记的13C标记K15多糖。 该多糖被用来开发有用的三维核磁共振技术 用于多糖的结构分析。 为制备A群脑膜炎奈瑟氏菌结合疫苗 并研究低聚糖的结构和大小对 免疫原性，并被设计用于化学合成 重复的低聚糖。该项目的第一阶段涉及 一种适当保护和活化的糖单体的合成。这个 N-乙酰甘露糖胺已成功引入以下基团 1-对甲氧基苄基、3-O-乙酰基、4-苄基、6-荧羧基。此外, 1-保护基已被选择性地移除。最后一步是 在1-位上加亚磷酰胺基团。在下一个时期 合适的连接臂将连接到受控孔玻璃上，并 单体将被构建在支架上。