a-GalCer is an immunostimulating glycolipid which is known to bind to CD Id molecule and activate invariant natural killer T (/NKT) cells. Herein, we report the synthesis and in vitro evalualuation of a-GalCer analogs with modification at the acylside chain or/and galactose-6' position. Substitutions at galaciactose-6' of a-GalCer had a dominant effect on the NKT and T cell receptor (TCR) recognition, remarkably Gal 6'-phenylacetamide substituted with either p-nitro, p-tert-butyl, or (o, m)-methyl were four times more selective for T helper 1 (TH1) cytokine secretion against a-GalCer. These new glycolipids may find use as adjuvants or as antimetastatic agents.
