Synthesis of a dimeric monosaccharide lipid A mimic and its synergistic effect on the immunostimulatory activity of lipopolysaccharide

Carbohydr Res. 2011 Sep 27;346(13):1705-13. doi: 10.1016/j.carres.2011.05.018. Epub 2011 May 26.

Abstract

Bacterial endotoxin lipopolysaccharide (LPS) is a potent immune stimulant, with the recognition of LPS and its active principal lipid A mediated by the Toll-like receptor 4 (TLR4)/MD-2 receptor complex. Due to the broad downstream implications of TLR4-mediated signalling, TLR4 ligands show great potential for immunotherapeutic manipulations. In this paper a dimeric monosaccharide lipid A mimic (3) has been designed as a potential TLR4 ligand. The chemical synthesis and the preliminary biological studies are described. Compound 3 shows a significant synergistic effect on LPS-induced ICAM-1 expression in human monocytic THP-1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Carbohydrate Sequence
  • Cell Line, Tumor
  • Drug Synergism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipid A / analogs & derivatives
  • Lipid A / chemistry*
  • Lipid A / pharmacology*
  • Lipopolysaccharides / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Toll-Like Receptor 4 / metabolism

Substances

  • Adjuvants, Immunologic
  • Lipid A
  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • Intercellular Adhesion Molecule-1