title: Antiviral and immunomodulating activities of chemically synthesized lipid A-subunit analogues GLA-27 and GLA-60.
abstract: Biological and antiviral activities of chemically synthesized lipid A-subunit analogues, GLA-27 and GLA-60, were investigated with respect to defense mechanisms such as macrophage and natural killer (NK) cell activation and interferon (IFN)-inducing activity. GLA-27, a 4-O-phosphono-D-glucosamine derivative carrying 3-O-tetradecanoyl (C14) and 2-N-3-tetradecanoyloxytetradecanoyl (C14-O-(C14] group, and GLA-60, a similar analogue carrying 3-O-linked C14-O-(C14) and 2-N-linked 3-hydroxytetradecanoyl (C14-OH) groups, strongly inhibited the formation of pox tail lesions and the growth of vaccinia virus at the tail lesion sites in infected mice. The antiviral activity of GLA-60 was about 1000-fold higher than that of muramyldipeptide (MDP), a representative immunomodulator. GLA-27 and GLA-60 had stronger immunomodulating activity than MDP in macrophage activation, NK cell activation and IFN-inducing activity, although it was weaker than natural lipid A. Toxic manifestations such as pyrogenicity, local Schwartzman reaction and lethality were far less pronounced for GLA-27 and GLA-60 than for natural lipid A.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.forename: C
authors.initials: C
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Nakatsuka
authors.forename: J Y
authors.initials: JY
authors.lastname: Homma
authors.forename: M
authors.initials: M
authors.lastname: Kiso
authors.forename: A
authors.initials: A
authors.lastname: Hasegawa
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000276:Adjuvants, Immunologic; D000818:Animals; D000998:Antiviral Agents; D005260:Female; D066298:In Vitro Techniques; D007369:Interferon Inducers; D007694:Killer Cells, Natural / Q000187:drug effects; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D011817:Rabbits; D014616:Vaccinia virus / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007369:Interferon Inducers; D008050:Lipid A; C056260:GLA 60; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C048988:GLA 27