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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.
AuthorsS Ikeda, C Nishimura, M Nakatsuka, J Y Homma, M Kiso, A Hasegawa
JournalAntiviral research (Antiviral Res) 1988 Jan-Feb Vol. 9 Issue 1-2 Pg. 37-46 ISSN: 0166-3542 [Print] NETHERLANDS
PMID3389769 (Publication Type: Journal Article)
Chemical References
  • Adjuvants, Immunologic
  • Antiviral Agents
  • Interferon Inducers
  • Lipid A
  • GLA 60
  • Acetylmuramyl-Alanyl-Isoglutamine
  • GLA 27
Topics
  • Acetylmuramyl-Alanyl-Isoglutamine (pharmacology)
  • Adjuvants, Immunologic
  • Animals
  • Antiviral Agents
  • Female
  • In Vitro Techniques
  • Interferon Inducers
  • Killer Cells, Natural (drug effects)
  • Lipid A (analogs & derivatives, pharmacology, toxicity)
  • Macrophage Activation (drug effects)
  • Male
  • Mice
  • Rabbits
  • Vaccinia virus (drug effects)

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