Lipid length and iso-branching of trehalose diesters influences Mincle agonist activity
Lipid length and iso-branching of trehalose diesters influences Mincle agonist activity
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DOI：
10.1016/j.tet.2017.11.076
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发表时间：
2018-03-22
期刊：
影响因子：
2.1
通讯作者：
Stocker, Bridget L.
中科院分区：
文献类型：
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作者：
Khan, Ayesha;Kodar, Kristel;Stocker, Bridget L.
我们报告了线性海藻糖二酯 (TDE) 和异支化 TDE（maradolipids 或 iso-TDE）的有效合成，以及它们激活骨髓源性巨噬细胞 (BMDM) 的能力（由细胞因子（IL-1 beta、IL-12、IL-6、IL-10）和趋化因子 (MIP-2) 的产生确定）。研究发现，两类 TDE 均以 Mincle 依赖性方式激活 BMDM，长链 (>= C18) 脂质会导致强烈的炎症反应。总体而言，与线性 TDE 相比，异支化 TDE 导致更多的细胞因子产生和更快的免疫反应。此外，C12-TDE 和 iso-C12-TDE 引发了 BMDM 产生 MIP-2，从而提供了第一个链长为 TDE 的例子
We report on the efficient synthesis of linear trehalose diesters (TDEs) and iso-branched TDEs (maradolipids or iso-TDEs) and their ability to activate bone marrow-derived macrophages (BMDMs) as determined by cytokine (IL-1 beta, IL-12, IL-6, IL-10) and chemokine (MIP-2) production. Both classes of TDEs were found to activate BMDMs in a Mincle-dependent manner, with longer-chain (>= C18) lipids leading to a robust inflammatory response. On the whole, the iso-branched TDEs led to greater cytokine production and a faster immune response when compared to their linear counterparts. Moreover, C12-TDE and iso-C12-TDE elicited the production of MIP-2 by BMDMs, thereby providing the first example of TDEs with a chain length of