Effect of dimerization of the D-glucose analogue of muramyl dipeptide on stimulation of macrophage-like cells.
N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) is the minimum required structure responsible for the immunoadjuvant activity of the bacterial cell wall. The D-glucose analogue of MDP (GADP) was reported to show a higher immunoadjuvant activity than MDP itself. Although the mechanism of activation by MDP and the existence of receptor against MDP are not clear, the patch formation and cluster formation of receptors are important steps on the signal transduction by such bioactive molecules. It is expected that the cluster effect such as antennary oligosaccharides reported by Lee et al. increased the affinity of ligand against receptor and accelerated the patch formation and cluster formation of receptors. In order to discuss the effect of multivalent-ligand formation of GADP on the activation of immunocompetent cells in more detail, we have synthesized GADP dimers combined through various lengths of alkyl and poly(ethylene glycol) (PEG) spacer groups as the simple models of multivalent-ligand molecule of GADP and evaluated their immunological enhancement activities in vitro. The GADP dimers showed a higher level stimulatory activities against macrophage-like cells than free GADP and monomeric GADP derivatives.
Murata
J
J
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Osaka, Japan.
Kitamoto
T
T
Ohya
Y
Y
Ouchi
T
T
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019281:Dimerization; D005947:Glucose; D018922:HL-60 Cells; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D011092:Polyethylene Glycols; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate