• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemistry: A European journal >Synthesis and biological evaluation of phosphono analogues of capsular polysaccharide fragments from Neisseria meningitidis A
【24h】

Synthesis and biological evaluation of phosphono analogues of capsular polysaccharide fragments from Neisseria meningitidis A

机译：脑膜炎奈瑟氏球菌A荚膜多糖片段的膦酰基类似物的合成及生物学评价

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Neisseria meningitidis type A (MenA) is a Gram-negative encapsulated bacterium that may cause explosive epidemics of meningitis, especially in the sub-Saharan region of Africa. The development and manufacture of an efficient glycoconjugate vaccine against Neisseria meningitidis A is greatly hampered by the poor hydrolytic stability of its capsular polysaccharide, which is made up of (1 -> 6)-linked 2-acetamido-2-deoxy-alpha-D-mannopyra-nosyl phosphate repeating units. Since this chemical lability is a product of the inherent instability of the phosphodiester bridges, here we report the synthesis of phosphonoester-linked oligomers of N-acetyl mannosamine as candidates for stabilised analogues of the corresponding phosphate-bridged saccharides. The installation of each interglycosidic phosphonoester linkage was achieved by Mitsunobu coupling of a glycosyl C-phosphonate building block with the 6-OH moiety of a mannosaminyl residue. Each of the synthesised compounds contains an O-linked aminopropyl spacer at its reducing end (alpha- or beta-oriented) to allow for protein conjugation. The relative affinities of the synthetic molecules were investigated by a competitive ELISA assay and showed that a human polyclonal anti-MenA serum can recognise both the phosphonoester-bridged fragments 1-3 and their monomeric subunits, glycosides 20 and 21. Moreover, the biological results suggest that the abilities of these compounds to inhibit the binding of a specific antibody to MenA polysaccharide are dependent on the chain lengths of the molecules, but independent on the orientations of the anomeric linkers.
机译：A型脑膜炎奈瑟氏球菌（MenA）是一种革兰氏阴性封装的细菌，可能引起脑膜炎的爆发性流行，尤其是在非洲撒哈拉以南地区。一种有效的针对脑膜炎奈瑟氏球菌A的糖缀合物疫苗的开发和生产因其荚膜多糖的水解稳定性差而受到阻碍，该荚膜多糖由（1-> 6）连接的2-acetamido-2-deoxy-alpha-D组成-甘露吡喃糖基磷酸酯重复单元。由于这种化学不稳定性是磷酸二酯桥固有稳定性的产物，因此我们在此报道了N-乙酰甘露糖胺的膦酸酯连接的低聚物的合成，作为相应的磷酸桥糖的稳定类似物的候选物。通过糖基C-膦酸酯结构单元与甘露糖胺基残基的6-OH部分的Mitsunobu偶联来实现每个糖苷间磷酸酯键的安装。每种合成的化合物在其还原末端（α-或β-定向）均包含一个O-连接的氨基丙基间隔基，以允许蛋白质结合。通过竞争性ELISA试验研究了合成分子的相对亲和力，结果表明，人多克隆抗MenA血清可以识别膦酸酯桥连的片段1-3及其单体亚基糖苷20和21。此外，生物学结果提示这些化合物抑制特异性抗体与MenA多糖结合的能力取决于分子的链长，但与异头连接体的方向无关。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号