Phosphatidylinositol mannoside ether analogues: syntheses and interleukin-12-inducing properties

J Org Chem. 2007 Jul 6;72(14):5291-6. doi: 10.1021/jo070639m. Epub 2007 Jun 9.

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 ether analogues 2 and 3 and evaluate their interleukin-12 (IL-12)-inducing properties along with dipalmitoyl PIM2 (1) in an in vitro bovine dendritic cell assay. Both synthetic PIM analogues and synthetic dipalmitoyl PIM2 (1) were effective at enhancing IL-12 production by immature bovine dendritic cells. Unexpectedly, ether analogue 2 was significantly more active than dipalmitoyl PIM2 (1) which indicates that modified PIM compounds can be strongly immunoactive and may have significant adjuvant activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Interleukin-12 / biosynthesis*
  • Molecular Structure
  • Phosphatidylinositols / chemical synthesis
  • Phosphatidylinositols / chemistry*
  • Phosphatidylinositols / pharmacology*

Substances

  • Phosphatidylinositols
  • phosphatidylinositol mannoside
  • Interleukin-12