SYNTHESIS OF MURAMYL DIPEPTIDE ANALOG-GLUCOMANNAN CONJUGATE AND ITS STIMULATION ACTIVITY AGAINST MACROPHAGE-LIKE CELLS

Since the mannose receptors exist on the surface of macrophages, the b ranched mannose residues of glucomannan are expected to act as targeti ng moieties to macrophages. So, in order to achieve an efficient deliv ery of D-glucose analogue of muramyl dipeptide (GADP) via receptor-med iated endocytosis by mannose receptors on the surface of macrophages, the GADP/carboxymethyl(CM)-glucomannan conjugate was synthesized. More over, in order to study the relationship between the immunological enh ancement activity of the conjugates and their mannose residues, we syn thesized the GADP/CM-glucomannan conjugates having various degrees of substitution of carboxymethyl group in mol% per sugar unit (DCM) and G ADP/CM-dextran conjugate through hybridization of GADP with dextran. T he immunological enhancement activities of GADP/CM-glucomannan conjuga tes and GADP/CM-dextran conjugate were evaluated by measurements of th e glucose consumption, the superoxide anion production and the beta-D- glucuronidase activity from PMA (phorbol-12-myristate-13-acetate)-diff erentiated HL-60 (human promyelocytic leukemia) or U937 (human monobla st leukemia) cells as macrophage-like cells. Copyright (C) 1996 Elsevi er Science Ltd