Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity.
Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity.
复制标题
DOI：
10.1038/ncomms8239
复制
发表时间：
2015-06-03
影响因子：
16.6
通讯作者：
Hung, Shang-Cheng
中科院分区：
文献类型：
--
作者：
Patil, Pratap S.;Cheng, Ting-Jen Rachel;Zulueta, Medel Manuel L.;Yang, Shih-Ting;Lico, Larry S.;Hung, Shang-Cheng
结核病是一个影响数百万人的全球性问题，由于耐药菌株和艾滋病毒共同感染结核分枝杆菌而加剧。磷脂酰肌醇甘露糖苷具有重要的免疫调节作用，是对M.结核病在宿主体内在这里，我们报告的高度复杂的四酰化磷脂酰肌醇六甘露糖苷（Ac 2 PIM 6），具有硬脂酸和tuberculostearic酸作为脂质成分的第一个合成。我们的工作是利用立体电子和空间效应来控制区域选择性和立体选择性的结果，并减少合成步骤，特别是在关键的去对称化和功能化的肌醇。本文还介绍了由罗氏酯经六步合成结核硬脂酸的方法。暴露于合成的Ac 2 PIM 6的小鼠表现出白细胞介素-4和干扰素-γ的产生增加，并且通过诱导卵清蛋白和破伤风类毒素特异性抗体显示出相应的佐剂效应。 磷脂酰肌醇甘露糖苷是对M.结核在这里，作者报告了一个优雅的和收敛的复杂糖脂四酰化磷脂酰肌醇六甘露糖苷（Ac 2 PIM 6）的全合成，并研究在小鼠中的免疫效果。
Tuberculosis, aggravated by drug-resistant strains and HIV co-infection of the causative agent Mycobacterium tuberculosis, is a global problem that affects millions of people. With essential immunoregulatory roles, phosphatidylinositol mannosides are among the cell-envelope components critical to the pathogenesis and survival of M. tuberculosis inside its host. Here we report the first synthesis of the highly complex tetraacylated phosphatidylinositol hexamannoside (Ac2PIM6), having stearic and tuberculostearic acids as lipid components. Our effort makes use of stereoelectronic and steric effects to control the regioselective and stereoselective outcomes and minimize the synthetic steps, particularly in the key desymmetrization and functionalization of myo-inositol. A short synthesis of tuberculostearic acid in six steps from the Roche ester is also described. Mice exposed to the synthesized Ac2PIM6 exhibit increased production of interleukin-4 and interferon-γ, and the corresponding adjuvant effect is shown by the induction of ovalbumin- and tetanus toxoid-specific antibodies. Phosphatidylinositol mannosides are cell envelope components vital for the survival of M. tuberculosis. Here, the authors report an elegant and convergent total synthesis of the complex glycolipid tetraacylated phosphatidylinositol hexamannoside (Ac2PIM6) and study the immunological effects in mice.
登录
查看更多内容
影响因子：
2.7
作者：
Jayaprakash, KN;Lu, J;Fraser-Reid, B
通讯作者：
Fraser-Reid, B
影响因子：
3.5
作者：
Ainge, Gary D.;Hudson, Jennifer;Harper, Jacquie L.
通讯作者：
Harper, Jacquie L.
影响因子：
15
作者：
Boonyarattanakalin, Siwarutt;Liu, Xinyu;Seeberger, Peter H.
通讯作者：
Seeberger, Peter H.
影响因子：
3.1
作者：
Kaeothip, Sophon;Demchenko, Alexei V.
通讯作者：
Demchenko, Alexei V.
影响因子：
3.5
作者：
Ainge, Gary D.;Parlane, Natalie A.;Painter, Gavin F.
通讯作者：
Painter, Gavin F.