Synthesis and human NKT cell stimulating properties of 3-O-sulfo-alpha/beta-galactosylceramides.
Two novel hybrid molecules 3-O-sulfo-alpha/beta-galactosylceramide 3 and 4, which are derived from an immunostimulatory agent alpha-GalCer 1 and self-glycolipid ligand sulfatide 2, were designed and synthesized. Compound 3 was shown to efficiently stimulate human NKT cells to secret IL-4 and IFN-gamma, with activities similar to 1, suggesting that modification of the 3''-OH position of the galactose moiety with sulfate has no significant effect on NKT cell stimulation. As a comparison, the beta-isomer 4 has no affinity to NKT cells, which demonstrates that the alpha-glycosidic bond of galactosylceramide is crucial to the NKT cells activation.
Xing
Guo-Wen
GW
Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Wu
Douglass
D
Poles
Michael A
MA
Horowitz
Amir
A
Tsuji
Moriya
M
Ho
David D
DD
Wong
Chi-Huey
CH
D002460:Cell Line; D015195:Drug Design; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism
D005699:Galactosylceramides; D015847:Interleukin-4; D007371:Interferon-gamma