CHEMISTRY OF THE POLYSACCHARIDE OF V CHOLERAE 0139

霍乱弧菌多糖的化学性质 0139

• 批准号: 6138646
• 负责人: C. ALLEN BUSH
• 金额: $ 16.23万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE COUNTY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138646
• 关键词: Vibrio cholerae; bacterial polysaccharides; carbohydrate structure; chemical models; cholera vaccine; computer simulation; conformation; epitope mapping; genetic strain; nuclear magnetic resonance spectroscopy; oligosaccharides; vaccine development

DESCRIPTION (Adapted from abstract): Strain O139 of Vibrio cholerae, identified as a cause of epidemic cholera in Asia, is encapsulated, which raises serious public health concerns. This pathogen is antigenically distinct from O1 strains. The applicant has reported on the covalent chemical structure of the polysaccharide capsule and has initiated studies on the polysaccharide as a vaccine component. A working hypothesis concerning the polysaccharide is that based on analogy to similar epitopes found in Lewis blood group oligosaccharides, four of the six sugar residues in the repeating subunit, adopt a well defined fixed conformation with the linkages to the other two residues forming a flexible hinge. Tests of this idea will involve computer molecular modeling and NMR measurements involving isotope enrichment in 13C and 15N to facilitate approach to structural and dynamics issues. Long range carbon coupling constants, 3JHC and 3JCC, will be measured and correlated with glycosidic dihedral angles. Three-dimensional heteronuclear NMR spectroscopy will provide enhanced spectral resolution in NOESY experiments. Polysaccharide dynamics will be investigated by indirectly measured heteronuclear 13C and 15N relaxation rates, which will be interpreted using spectral density mapping methods as well as several forms of the model-free treatment augmented to include anisotropic tumbling and slower exchange processes. Oligosaccharide fragments will test the hypothesis of a conformational epitope that depends on molecular size. The oligosaccharides are to be used in development of chemically modified protein conjugates for vaccine development.

描述（改编自摘要）： 霍乱弧菌O139菌株，被确定为流行病的原因 霍乱在亚洲，是封装，这引起了严重的公共卫生 性问题该病原体在抗原性上不同于O1菌株。的 申请人已经报道了该化合物的共价化学结构， 多糖胶囊，并启动了对多糖的研究 作为疫苗的一部分。一个关于 多糖是基于类似的抗原决定基发现， 刘易斯血型低聚糖，六个糖残基中的四个， 重复亚基采用明确的固定构象， 与其他两个残基的连接形成柔性铰链。试验 这个想法将涉及计算机分子建模和核磁共振测量 涉及13C和15N的同位素富集， 结构和动力问题。长程碳偶合常数， 3JHC和3JCC将被测量并与糖苷二面体相关 的角度三维异构NMR光谱将提供 NOESY实验中增强的光谱分辨率。多糖 动力学将通过间接测量的13 C异质结进行研究 和15N弛豫率，这将被解释使用光谱 密度映射方法以及几种形式的无模型 增强处理，包括各向异性翻滚和较慢的交换 流程.寡糖片段将检验 依赖于分子大小的构象表位。的 低聚糖将用于开发化学修饰的 用于疫苗开发的蛋白质缀合物。