DESIGN OF MACROMOLECULAR BIOLOGICAL RESPONSE MODIFIER BY IMMOBILIZINGOF D-GLUCOSE ANALOG OF MURAMYL DIPEPTIDE ON CARBOXYMETHYL-DEXTRAN HAVING MANNOSE BRANCHES

It is well known that muramyl dipeptide is a minimum required structur e of bacterial peptidoglycan responsible for immunoadjuvant activity. Since mannose receptors exist on the surface of macrophages, polymers with branched mannose residues are expected to target moieties to macr ophages. To achieve an efficient delivery of D-glucose analogue of mur amyl dipeptide (GADP) via receptor-mediated endocytosis by mannose rec eptors on the surface of macrophages, GADP/carboxymethyl-dextran (CM-D ex)/Man conjugate was synthesized. Moreover, to study the effect of th e introduction of mannose residues, we also synthesized GADP/CM-glucom annan (CM-GM) and GADP/CM-Dex conjugates. The immunological enhancemen t activities of their conjugates were evaluated by measurements of glu cose consumption and beta-D-glucuronidase activity from macrophage-lik e cells. The GADP/CM-Dex/Man and GADP/CM-GM conjugates showed higher i mmunological enhancement activity than the GADP/CM-Dex conjugate. The immunological enhancement activity of GADP/CM-Dex/Man and GADP/CM-GM c onjugates was decreased to the same level of immunological enhancement activity of GADP/CM-Dex conjugate under the presence of excess mannos e. These results suggested that the introduction of mannose residues i nto GADP/CM-Dex conjugate could increase the affinity against macropha ge and the immunological enhancement activity of GADP/CM-Dex conjugate itself.