Synthesis and Evaluation of 1,2,3-Triazole Containing Analogues of the Immunostimulant α-GalCer

α-GalCer is the first defined and most potent agonistic antigen of the T cell receptor of natural killer T cells. We have prepared a series of 1,2,3-triazole-containing α-GalCer analogues in which the lipid chain lengths have been incrementally varied. We found that this isosteric replacement of α-GalCer's amide moiety with triazole increases the IL-4 versus IFN-γ bias of released cytokines. The stimulatory effect was influenced by the length of the attached chain. In particular, the long-chained triazole analogues have a comparable stimulatory effect on cytokine production as α-GalCer and exhibit a stronger Th2 cytokine response.