Synthesis and biological activity of ester and ether analogues of alpha-galactosylceramide (KRN7000)

Carbohydr Res. 2010 Aug 16;345(12):1663-84. doi: 10.1016/j.carres.2010.05.003. Epub 2010 May 12.

Abstract

Alpha-Galactosylceramide (alphaGalCer, KRN7000) has been identified as a modulator of immunological processes through its capacity to bind iNKT cells mediated by CD1d molecules. Some analogues in while the amide group in alphaGalCer is replaced with ester or ether groups were synthesized from d-arabinitol or l-ribose to evaluate their ability to activate iNKT cells. Ester analogues 30a, 31a, and 61 showed activity for IFNgamma and IL-4 production of iNKT cells, while ether (31b) and 4-methoxy ester (76) analogues of alpha-galactosylceramide were not active for iNKT cells.

MeSH terms

  • Animals
  • Esters / chemical synthesis
  • Esters / chemistry
  • Esters / pharmacology*
  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Ethers / pharmacology*
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / chemistry
  • Galactosylceramides / pharmacology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / blood
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / blood
  • Mice
  • Molecular Conformation
  • Natural Killer T-Cells / drug effects*
  • Natural Killer T-Cells / immunology
  • Stereoisomerism

Substances

  • Esters
  • Ethers
  • Galactosylceramides
  • Interleukin-4
  • Interferon-gamma
  • KRN 7000