Synthesis and in vitro evaluation of alpha-GalCer epimers

ChemMedChem. 2008 Jul;3(7):1061-70. doi: 10.1002/cmdc.200800021.

Abstract

alpha-GalCer (also known as KRN7000) is an immunomodulatory glycolipid that is known to potently activate invariant natural killer T (NKT) cells upon CD1d-mediated stimulation. Because Th1 and Th2 cytokines, which are released after alpha-GalCer presentation, antagonize each other's effects, alpha-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. In this context, we report the synthesis and in vitro evaluation of alpha-Gal-D-xylo-Cer and two alpha-Gal-L-lyxo-Cer analogues, one with the natural acyl chain, the other with a truncated chain.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1
  • Cytokines / immunology
  • Cytokines / metabolism
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / pharmacology*
  • Glycolipids / chemical synthesis
  • Glycolipids / pharmacology*
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Spleen / cytology
  • Spleen / drug effects*
  • Spleen / metabolism
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Antigens, CD1
  • Cytokines
  • Galactosylceramides
  • Glycolipids
  • alpha-galactosylceramide
  • KRN 7000