Genomics Research Center, Academia Sinica, Nankang District, Taipei, Taiwan.
Antimicrob Agents Chemother. 2010 Oct;54(10):4129-36. doi: 10.1128/AAC.00368-10. Epub 2010 Jul 26.
Alpha-galactosyl ceramide (α-GalCer) has been known to bind to the CD1d receptor on dendritic cells and activate invariant natural killer T (iNKT) cells, which subsequently secrete T-helper-cell 1 (Th1) and Th2 cytokines, which correlate with anti-infection activity and the prevention of autoimmune diseases, respectively. α-GalCer elicits the secretion of these two cytokines nonselectively, and thus, its effectiveness is limited by the opposing effects of the Th1 and Th2 cytokines. Reported here is the synthesis of a new α-GalCer analog (compound C34), based on the structure of CD1d, with a 4-(4-fluorophenoxy) phenyl undecanoyl modification of the N-acyl moiety of α-GalCer. Using several murine bacterial and viral infection models, we demonstrated that C34 has superior antibacterial and antiviral activities in comparison with those of several other Th1-selective glycolipids and that it is most effective by administering it to mice in a prophylactic manner before or shortly after infection.
α-半乳糖神经酰胺（α-GalCer）已被证实可与树突状细胞上的 CD1d 受体结合，激活不变自然杀伤 T（iNKT）细胞，随后分泌 T 辅助细胞 1（Th1）和 Th2 细胞因子，分别与抗感染活性和预防自身免疫性疾病相关。α-GalCer 非选择性地引发这两种细胞因子的分泌，因此，其有效性受到 Th1 和 Th2 细胞因子的相反作用的限制。本文报道了一种基于 CD1d 结构的新型 α-GalCer 类似物（化合物 C34）的合成，其 N-酰基部分的 4-（4-氟苯氧基）苯基十一烷酰修饰。使用几种小鼠细菌和病毒感染模型，我们证明 C34 与几种其他 Th1 选择性糖脂相比具有更好的抗菌和抗病毒活性，并且通过在感染前或感染后不久以预防性方式给予小鼠，其效果最佳。
