α-N-Cyc-Cer

A series of α-GalCer analogues with modified α-glycosidic linkages were tested for their ability to stimulate splenic NKT cell proliferation and cytokine production. These α-glycoside analogues included α-C-GalCer with a CH2 group in place of the glycosidic oxygen atom; a nonisosteric analogue that has one less CH2 group than α-C-GalCer in the link between the sugar and the sphingolipid (α-1C-GalCer); a compound with a rigid triple bond in the link between the sugar and sphingolipid (α-C-alkyne-GalCer); a variant bearing an ether oxygen atom in the linker (α-C-O-GalCer); and an aminocyclitol variant (α-N-Cyc-Cer). NKT cells respond to a variety of CD1d-restricted glycolipid antigens that are structurally related to the prototypic antigen, α-galactosylceramide (α-GalCer). A modified analogue of α-GalCer with a carbon-based glycosidic linkage (α-C-GalCer) has generated great interest because of its apparent ability to promote prolonged, Th1-biased immune responses.