title: Immunopharmacological activities of 2-keto-3-deoxyoctonic acid-(alpha 2----6)-linked 4-O-phosphono-D-glucosamine derivatives carrying N- and 3-O-acyl substituents.
abstract: The immunopharmacological activities of 2-keto-3-deoxyoctonic acid (KDO)-(alpha 2----6)-linked lipid A-subunit analogs, 4-O-phosphono-D-glucosamine derivatives carrying N- and 3-O-acyl substituents, were compared with those of the corresponding analogs without KDO, GLA-27, GLA-47, and GLA-60. Among the analogs tested, GLA-60, a 4-O-phosphono-D-glucosamine carrying N-3-hydroxytetradecanoyl and 3-O-3-tetradecanoyloxytetradecanoyl groups, exhibited the most intensive activities in terms of mitogenicity, adjuvanticity, and mediator (tumor necrosis factor and colony-stimulating factor) induction. Binding (alpha 2----6) of KDO to GLA-60 failed to enhance the activities. Similarly, the activities of GLA-27 and GLA-47 were also decreased by introduction of KDO to the O-6 of the analogs. This indicates that the strengths of the activities of the subunit analogs depend on the kinds of N- and 3-O-linked acyl substituents and not on the presence of the KDO linked to the O-6.
authors: School of Pharmaceutical Sciences, Kitasato University, Japan.
authors: Y
authors: Y
authors: Kumazawa
authors: M
authors: M
authors: Matsuura
authors: J Y
authors: JY
authors: Homma
authors: T
authors: T
authors: Furuya
authors: H
authors: H
authors: Takimoto
authors: K
authors: K
authors: Inagaki
authors: T
authors: T
authors: Nagumo
authors: M
authors: M
authors: Kiso
authors: A
authors: A
authors: Hasegawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003115:Colony-Stimulating Factors / Q000032:analysis; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008934:Mitogens / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013400:Sugar Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D008050:Lipid A; D008934:Mitogens; D013400:Sugar Acids; D014409:Tumor Necrosis Factor-alpha; C002532:2-keto-3-deoxyoctonate