Synthesis of muramyl dipeptide analogue—glucomannan conjugate and its stimulation activity against macrophage-like cells

Abstract

Since the mannose receptors exist on the surface of macrophages, the branched mannose residues of glucomannan are expected to act as targeting moieties to macrophages. So, in order to achieve an efficient delivery of d-glucose analogue of muramyl dipeptide (GADP) via receptor-mediated endocytosis by mannose receptors on the surface of macrophages, the GADP/carboxymethyl(CM)-glucomannan conjugate was synthesized. Moreover, in order to study the relationship between the immunological enhancement activity of the conjugates and their mannose residues, we synthesized the GADP/CM-glucomannan conjugates having various degrees of substitution of carboxymethyl group in mol% per sugar unit (DCM) and GADP/CM-dextran conjugate through hybridization of GADP with dextran. The immunological enhancement activities of GADP/CM-glucomannan conjugates and GADP/CM-dextran conjugate were evaluated by measurements of the glucose consumption, the superoxide anion production and the β- d-glucuronidase activity from PMA (phorbol-12-myristate-13-acetate)-differentiated HL-60 ( human promyelocytic leukemia) or U937 ( human monoblast leukemia) cells as macrophage-like cells.