ABSTRACT
N-Acetyl-d-glucosamine branches were incorporated at the C-6 position of curdlan, a linear ß-1,3-d-glucan, and the resulting nonnatural branched polysaccharides were evaluated in terms of the immunomodulation activities in comparison with lentinan, a ß-1,3-d-glucan having d-glucose branches at C-6. To incorporate the amino sugar branches, we conducted a series of regioselective protection-deprotections of curdlan involving triphenylmethylation at C-6, phenylcarbamoylation at C-2 and C-4, and detriphenylmethylation. Subsequent glycosylation with a d-glucosamine-derived oxazoline, followed by deprotection gave rise to the branched curdlans with various substitution degrees. The products exhibited remarkable solubility in both organic solvents and water. Their immunomodulation activities were determined using mouse macrophagelike cells, and the secretions of both the tumor necrosis factor and nitric oxide proved to be significantly higher than those with lentinan. These results conclude that the amino sugar/curdlan hybrid materials are promising as a new type of polysaccharide immunoadjuvants useful for cancer chemotherapy.
Subject(s)
Adjuvants, Immunologic/chemical synthesis , Biomimetic Materials/chemical synthesis , Immunologic Factors/chemical synthesis , Lentinan/chemistry , Macrophages/immunology , beta-Glucans/chemistry , Acetylglucosamine/chemistry , Adjuvants, Immunologic/pharmacology , Animals , Biomimetic Materials/pharmacology , Carbohydrate Sequence , Cell Line , Glucose/chemistry , Glycosylation , Immunologic Factors/pharmacology , Lentinan/immunology , Lentinan/pharmacology , Macrophage Activation/drug effects , Macrophages/drug effects , Magnetic Resonance Spectroscopy , Methylation , Mice , Molecular Mimicry/immunology , Molecular Sequence Data , Nitric Oxide/biosynthesis , Solubility , Tumor Necrosis Factor-alpha/biosynthesis , beta-Glucans/immunology , beta-Glucans/pharmacologyABSTRACT
In view of the interesting properties of branched polysaccharides occurring in nature, biological activities of nonnatural branched chitins having beta-1,6-N-acetyl-D-glucosamine branches on the poly(beta-1,4-N-acetyl-D-glucosamine) backbone have been studied. The immunostimulatory activities of the branched chitins were determined and compared with those of lentinan, a beta-1,3-D-glucan having beta-1,6-D-glucose branches, using the mouse macrophagelike cell line RAW264.7 in vitro. The secretions of the tumor necrosis factor and nitric oxide proved to be significantly higher with the branched chitins than with lentinan. Moreover, when interferon-gamma was used in conjunction with the branched chitins on macrophage treatment, a marked augmentation of nitric oxide production was observed. These results are interpreted as the direct stimulation of macrophages by the branched chitins, and the distinctive activities suggest the possibility of developing new types of polysaccharide antitumor agents.
