Synthesis of 5-Thio-α-GalCer Analogues with Fluorinated Acyl Chain on Lipid Residue and Their Biological Evaluation

Invariant natural killer T (iNKT) cells are a subclass of T cells that initiates the secretion of T helper 1 and 2 cytokines after recognizing CD1d protein presented glycolipid antigens. In this Letter, we designed and synthesized a novel series of CD1d ligand α-galactosylceramides (α-GalCers) in which the acyl chain backbone of the lipid was incorporated with fluorine atoms. The in vivo evaluation of immunostimulatory activities revealed that the synthesized α-5-thio-galactopyranosyl-N-perfluorooctanoyl phytosphingosine exhibited a remarkable potency toward selectively enhancing TH1 cytokine production with the IFN γ/IL-4 ratio of 9/1, while its perfluorotetradecanoyl counterpart showed TH2 profile with an IFN γ/IL-4 ratio of 0.59/1. The analogues synthesized here would be used as probes to study lipid–protein interactions in α-GalCer/CD1d complexes