title: Synthesis and macrophage activation of lentinan-mimic branched amino polysaccharides: curdlans having N-Acetyl-d-glucosamine branches.
abstract: N-Acetyl-d-glucosamine branches were incorporated at the C-6 position of curdlan, a linear β-1,3-d-glucan, and the resulting nonnatural branched polysaccharides were evaluated in terms of the immunomodulation activities in comparison with lentinan, a β-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.
authors.affiliation: Department of Materials and Life Science, Seikei University , Musashino-shi, Tokyo, Japan. kurita@st.seikei.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kurita
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahara
authors.forename: Kiyoshige
authors.initials: K
authors.lastname: Hatta
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimojoh
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002460:Cell Line; D005947:Glucose / Q000737:chemistry; D006031:Glycosylation; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000494:pharmacology; D007912:Lentinan / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D047071:beta-Glucans / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; D009569:Nitric Oxide; D007912:Lentinan; C038459:curdlan; D005947:Glucose; D000117:Acetylglucosamine