CHEMISTRY OF THE POLYSACCHARIDE OF V CHOLERAE 0139

说明(改编自摘要)： 霍乱弧菌O139菌株，被确认为流行原因 亚洲的霍乱病毒被封装，这会带来严重的公共卫生问题 担忧。这种病原体在抗原性上不同于O1菌株。这个 申请人已报告该化合物的共价化学结构 多糖胶囊，并开始了对多糖类的研究 作为疫苗的组成部分。一个工作假说，关于 多糖是一种基于与在 刘易斯血型低聚糖，六种糖中的四种 重复亚单位，采用明确的固定构象与 连接到另外两个残基，形成一个柔性铰链。测试 这一想法将涉及计算机分子建模和核磁共振测量 涉及13C和15N的同位素浓缩，以促进接近 结构和动力学问题。长程碳耦合常数， 3JHC和3JCC将被测量并与糖苷二面体相关联 天使。三维异核核磁共振波谱将提供 在NOESY实验中增强了光谱分辨率。多糖类 动力学将通过间接测量的异核13C进行研究 和15N驰豫速率，这将用光谱来解释 密度映射方法以及几种形式的无模型 强化治疗以包括各向异性翻滚和较慢的交换 流程。低聚糖片段将检验一个假说 取决于分子大小的构象表位。这个 低聚糖将用于化学改性的开发 用于疫苗开发的蛋白质结合物。

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.