title: Synthesis of a dimeric monosaccharide lipid A mimic and its synergistic effect on the immunostimulatory activity of lipopolysaccharide.
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.
authors.affiliation: Department of Chemistry, Lakehead University, Thunder Bay, Ontario, Canada.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Lewicky
authors.forename: Marina
authors.initials: M
authors.lastname: Ulanova
authors.forename: Zi-Hua
authors.initials: ZH
authors.lastname: Jiang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D008050:Lipid A; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D018799:Intercellular Adhesion Molecule-1