Introduction of aromatic group on 4'-OH of α-GalCer manipulated NKT cell cytokine production.
Introduction of aromatic group on 4'-OH of α-GalCer manipulated NKT cell cytokine production.
复制标题
在 α-GalCer 的 4-OH 上引入芳香族基团可操纵 NKT 细胞细胞因子的产生。
DOI：
10.1016/j.bmc.2010.11.061
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发表时间：
2011
影响因子：
3.5
通讯作者：
Wang,PengGeorge
中科院分区：
文献类型：
--
作者：
Zhang,Wenpeng;Xia,Chengfeng;Nadas,Janos;Chen,Wenlan;Gu,Li;Wang,PengGeorge
已发现鞘糖脂α-GalCer通过自然杀伤T细胞显著影响哺乳动物免疫系统。不幸的是，临床前和临床研究揭示了几个关键的缺点，阻碍了α-GalCer在治疗癌症和其他疾病中的治疗应用。近年来，对CD 1d/α-GalCer/NKT TCR复合物晶体结构的详细阐述，以及对糖脂配体和NKT细胞的结构和生物学方面的最新认识，为开发具有最佳治疗效果的新型糖脂配体提供了新的平台。本文设计了一系列新型的芳香族取代的α-GalCer类似物。这些类似物的生物活性进行了表征，结果表明，独特的取代基团操纵NKT细胞的免疫反应。计算机模拟研究表明，与α-GalCer相比，该类似物在形成CD 1d/糖脂/NKT TCR复合物时具有独特的结合模式。
The glycosphingolipid α-GalCer has been found to influence mammalian immune system significantly through the natural killer T cells. Unfortunately, the pre-clinical and clinical studies revealed several critical disadvantages that prevented the therapeutic application of α-GalCer in treating cancer and other diseases. Recently, the detailed illustration of the CD1d/α-GalCer/NKT TCR complex crystal structural, together with other latest structural and biological understanding on glycolipid ligands and NKT cells, provided a new platform for developing novel glycolipid ligands with optimized therapeutic effects. Here, we designed a series of novel aromatic group substituted α-GalCer analogues. The biological activity of these analogues was characterized and the results showed the unique substitution group manipulated the immune responses of NKT cells. Computer modeling and simulation study indicated the analogues had unique binding mode when forming CD1d/glycolipid/NKT TCR complex, comparing to original α-GalCer.