EFFECT OF DIMERIZATION OF THE D-GLUCOSE ANALOG 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 eel wall. The D-glucose analogue of MDP (GADP) was reported to show a higher immunoadjuvant activity than MDP itself, Although the mechanis m of activation by MDP and the existence of receptor against MDP are n ot clear, the patch formation and cluster formation of receptors are i mportant steps on the signal transduction by such bioactive molecules. It is expected that the cluster effect such as antennary oligosacchar ides reported by Lee et al. increased the affinity of ligand against r eceptor and accelerated the patch formation and cluster formation of r eceptors. In order to discuss the effect of multivalent-ligand formati on of GADP on the activation of immunocompetent cells in more detail, we have synthesized GADP dimers combined through various lengths of al kyl and poly(ethylene glycol) (PEG) spacer groups as the simple models of multivalent-ligand molecule of GADP and evaluated their immunologi cal enhancement activities in vitro. The GADP dimers showed a higher l evel stimulatory activities against macrophage-like cells than free GA DP and monomeric GADP derivatives. (C) 1997 Elsevier Science Ltd.