Synthesis and evaluation of an acyl-chain unsaturated analog of the Th2 biasing, immunostimulatory glycolipid, OCH

Bioorg Med Chem Lett. 2009 Jul 1;19(13):3386-8. doi: 10.1016/j.bmcl.2009.05.042. Epub 2009 May 18.

Abstract

An alpha-galactosyl ceramide (alpha-GalCer) 2 was synthesized and evaluated for its ability to stimulate iNKT-cell proliferation and elicit T-helper cytokines, IL-4 and IFNgamma. Compound 2 combines the acyl chain of the potent, Th2 biasing alpha-GalCer 1 with a sphingoid base of the same length as that found in OCH, which also exhibits Th2 skewing, Such complementation may enhance cytokine bias, which is thought to be important for therapeutic applications of iNKT cell stimulation. Two related alpha-GalCers, 3 and 4, with saturated acyl chains were prepared for comparison.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Alkanes / chemical synthesis*
  • Alkanes / chemistry
  • Alkanes / pharmacology
  • Animals
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism
  • Galactosylceramides / chemistry*
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Monosaccharides / chemical synthesis*
  • Monosaccharides / chemistry
  • Monosaccharides / pharmacology
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*

Substances

  • Adjuvants, Immunologic
  • Alkanes
  • Antigens, CD1d
  • Galactosylceramides
  • Monosaccharides
  • OCH compound
  • alpha-galactosylceramide
  • Interleukin-4
  • Interferon-gamma