Design and synthesis of new KRN7000 analogues

Presented by CD1d protein, KRN7000, a potent synthetic α-galactosylceramide, is known to stimulate the iNKT cells to produce different bioactive cytokines. Six new KRN7000 analogues, in which the amide bond in KRN7000 is replaced with O, NH, or ester groups incorporating variation of the acyl chain, or possessing an additional four-atom linker between the galactose and phytosphingosine moiety, were designed and synthesized. The synthetic compounds were evaluated for their ability to stimulate cytokine release and the preliminary structure–activity relationships were discussed. The synthetic strategy will benefit the construction of more KRN7000 derivatives, which may contribute to cytokine profile bias.