Phosphatidylinositol mannosides: synthesis and adjuvant properties of phosphatidylinositol di- and tetramannosides

Bioorg Med Chem. 2006 Nov 15;14(22):7615-24. doi: 10.1016/j.bmc.2006.07.003. Epub 2006 Jul 27.

Abstract

Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating properties. We present here the syntheses of phosphatidylinositol dimannoside (PIM2, 1) and phosphatidylinositol tetramannoside (PIM4, 2) and evaluate their adjuvant properties in a transgenic mouse model. The key step in the synthetic methodology for the synthesis of 2 relies on the selective glycosylation of diol 3 with mannosyl donor 11. Both synthetic PIMs were effective at enhancing IFN-gamma when given as adjuvants with a model antigen, with PIM2 being the more active. These data suggest that in this assay the PIM core structure is responsible for the observed biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis*
  • Adjuvants, Immunologic / chemistry
  • Animals
  • Carbohydrate Conformation
  • Mannosides / chemical synthesis*
  • Mannosides / chemistry
  • Mannosides / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • Phosphatidylinositols / chemical synthesis*
  • Phosphatidylinositols / chemistry
  • Phosphatidylinositols / immunology*

Substances

  • Adjuvants, Immunologic
  • Mannosides
  • Phosphatidylinositols
  • phosphatidylinositol dimannoside
  • Ovalbumin