Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3475-8. doi: 10.1016/j.bmcl.2010.05.010.

Abstract

Alpha-glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the alpha-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely alpha-selective and provided gram quantities of amine 11, from which alpha-glucosyl ceramides 4 and 5 were obtained by N-acylation. alpha-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. alpha-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2), induced extremely similar levels of iNKT cell activation and expansion.

Publication types

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

MeSH terms

  • Acylation
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Glucosylceramides / chemical synthesis*
  • Glucosylceramides / pharmacology*
  • Glycosylation
  • Humans
  • Lymphocyte Activation / drug effects
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / drug effects*
  • Structure-Activity Relationship

Substances

  • Glucosylceramides