School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Bioorg Med Chem Lett. 2012 Jul 1;22(13):4348-52. doi: 10.1016/j.bmcl.2012.05.009. Epub 2012 May 9.
Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.
6″-叠氮基-6″-去氧-α-半乳糖基神经酰胺 11 与一系列炔烃（或苯炔前体）的[3+2]双环加成反应以高产率得到了一系列含三唑的α-半乳糖基神经酰胺（α-GalCer）类似物。这些α-GalCer 类似物和前体叠氮化物 11 被测试其激活 iNKT 细胞并在体外刺激 IL-2 细胞因子分泌以及体内 IFN-γ 和 IL-4 细胞因子分泌的能力。这些类似物中的一些，特别是 11、12b、12f 和 13，比原型 CD1d 激动剂 α-GalCer 1 更能刺激 IL-2 的分泌。就任何细胞因子偏向而言，大多数含三唑的类似物相对于 α-GalCer 1 显示出较小的 Th2 细胞因子偏向反应。相比之下，环加成前体即叠氮化物 11 提供了较小的 Th1 细胞因子偏向反应。
