Synthesis and TNF-alpha inducing activities of mycoloyl-arabinan motif of mycobacterial cell wall components

Bioorg Med Chem. 2006 May 1;14(9):3049-61. doi: 10.1016/j.bmc.2005.12.037. Epub 2006 Jan 19.

Abstract

The extract of the cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) from Mycobacterium bovis is known to be an activator of innate immunity. Synthesis of pentaarabinofuranoside as part of the arabinan moiety of BCG-CWS was achieved by double alpha-arabinofuranosylation followed by double beta-arabinofuranosylation with orthogonally protected donors. Mycolic esters of the arabinan in the terminal lipo-arabinan motif of BCG-CWS were synthesized through alkylation of unprotected mycolic acid with bis- and tetra-tosylates of pentaarabinofuranoside. A series of compounds were subjected to a tumor necrosis factor alpha (TNF-alpha) secretion-inducing assay, disclosing aspects of the structure-activity relationship which should be useful in finding the site of the activity.

MeSH terms

  • Animals
  • Carbohydrate Conformation
  • Cell Line
  • Cell Wall / chemistry*
  • Cell Wall / metabolism*
  • Esterification
  • Mass Spectrometry
  • Mice
  • Mycobacterium bovis / chemistry*
  • Mycobacterium bovis / metabolism*
  • Mycolic Acids / chemistry
  • Polysaccharides / biosynthesis*
  • Polysaccharides / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Mycolic Acids
  • Polysaccharides
  • Tumor Necrosis Factor-alpha
  • araban