Design of d-glucose analogue of MDP/CM-curdlan conjugate and its immunological enhancement activity

Abstract

It is well known that N- acetylmuramyl- l-alanyl- d-isoglutamine (MDP) is a minimum required structure of bacterial peptidoglycan responsible for immunoadjuvant activity. Although MDP itself has no antitumor activity, the MDP derivatives modified with lipophilic groups are reported to exhibit antitumor activities in vivo. On the other hand, curdlan (normal chain (1 → 3)-β- d-glucan) is known to exhibit an antitumor activity through stimulation of the host immuno-system. In order to provide the novel synthetic biological response modifier exhibiting high antitumor activity, we synthesized a hybrid type conjugate of curdlan immobilizing d-glucose analogue of MDP (GADP). The immunological enhancement activity of the conjugate obtained was evaluated by the test of glucose consumption of DMSO-differentiated HL-60 ( human promyelocytic leukemia) cells, the test of superoxide anion (O 2−) production from PMA (phorbol-12-myristate-13-acetate)-differentiated HL-60 cells, and the test of cytotoxic factor production from PMA-differentiated U937 ( human monoblast leukemia) cells. These results suggested that the immunological enhancement activity of GADP was increased by the hybridization with curdlan.