NAT COMMUN:多糖人工合成取得突破性进展

2017-03-20 佚名 健康一线

北京大学天然药物及仿生药物国家重点实验室叶新山教授研究团队经过多年的研究积累,近期在多糖人工合成上取得突破性进展,其研究结果“由 92 个单糖单元组成的分枝杆菌阿拉伯半乳聚糖的全合成”,在糖合成领域具有里程碑式的意义,可望为复杂多糖的合成开启新的篇章。相关论文 3 月 16 日发表在国际顶级期刊《自然·通讯》上。

近期,北京大学天然药物及仿生药物国家重点实验室叶新山教授研究团队在多糖人工合成上取得突破性进展,其“由92个单糖单元组成的分枝杆菌阿拉伯半乳聚糖的全合成”在糖合成领域具有里程碑式的意义。



该研究人员从简单易得的单糖原料出发,采用他们前期所发展的基于糖基供体“预活化”的一釜寡糖合成策略,以克级规模实现了寡糖链的大量制备;并且利用构象受限的糖基供体高立体选择性地构建1,2-顺式糖苷键;随后再次使用“预活化”一釜寡糖合成策略分别完成了两条多糖链(A链和B链)的快速组装;最后采用他们自己发展的糖基化反应偶联剂,经[31+31+30]糖基化反应,顺利实现了高度分支化、由92个单糖单元所组成的阿拉伯半乳聚糖的首次全合成。

据叶新山介绍,如果将多糖的人工全合成比作建高楼的话,每一个单糖单元代表一层楼,此前世界纪录只能建到20层~30层,而北京大学天然药物及仿生药物国家重点实验室的这项研究使多糖这座大楼成功建造到92层。这是迄今人类所合成的最大、最复杂的均一结构的多糖分子,创造了新的世界纪录。

叶新山团队选取阿拉伯半乳聚糖这个多糖为目标分子。该分子由一条半乳聚糖链(A链)和两条紧密靠近的阿拉伯聚糖链(B链)所组成,具有高度分支的结构。

据了解,多糖是一类在生命体中发挥着重要作用的生物大分子,但多糖的结构却非常复杂,使多糖的合成难题长期以来一直困扰着合成化学家,令化学家望而却步,严重地制约着人们对多糖的生物学功能的认识以及实现它在改善人民生活质量方面的用途。

阿拉伯半乳聚糖是一种重要的多糖,它是结核分枝杆菌细胞壁的重要组成成分,与细菌的存活力和致病力密切相关。

该多糖的化学合成有助于开发预防结核病的新型糖疫苗,对解决日益凸显的结核菌耐药性问题具有重要意义。

原始出处:
Yong Wu, De-Cai Xiong, Si-Cong Chen et al. Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units. Nature Communication 8, 14851(2017).doi:10.1038/ncomms14851.

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    2017-07-31 liuli5079
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    2017-10-05 liye789132251
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    2017-03-21 dhzzm

    学习了,分享了

    0

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