Abstract |
Thirteen 6-O-acyl-N-acetylmuramyl-L-alanyl-D-isoglutamines (6-O-acyl-MDPs), including four inactive D-isoasparagine and L- isoglutamine analogs, were tested for their pyrogenicity and immunopotentiating activity to stimulate primary humoral and cellular immune responses in guinea pigs to a model protein antigen, ovalbumin, when administered in various vehicles. Among them, derivatives whose muramic acid residue was substituted by alpha-branched (and beta-hydroxylated) higher fatty acids at the carbon-6 position, especially 6-O-(2-tetradecylhexadecanoyl)-MDP (B3O-MDP) and, to a lesser extent, 6-O-(3-hydroxy-2-docosylhexacosanoyl)-MDP (BH48-MDP) and its L-serine analog [BH48-MDP(L-Ser)], were found to exert strong adjuvant activity in both the induction of delayed-type hypersensitivity and the stimulation of circulating precipitating antibody levels when combined with nonirritating vehicles ( liposomes, squalene-in-water emulsion, and phosphate-buffered saline). These vehicles did not efficiently support the adjuvant activity of MDP, the parent molecule of the above lipophilic derivatives. Pyrogenicity tests showed that introduction of alpha-branched higher fatty acid groups but not of straight, long-chain fatty acids at the 6-position of the muramic acid residue resulted in marked decrease of the pyrogenicity inherent to MDP via intravenous administration.
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Authors | M Tsujimoto, S Kotani, F Kinoshita, S Kanoh, T Shiba, S Kusumoto |
Journal | Infection and immunity
(Infect Immun)
Vol. 53
Issue 3
Pg. 511-6
(Sep 1986)
ISSN: 0019-9567 [Print] United States |
PMID | 3744548
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adjuvants, Immunologic
- Emulsions
- Liposomes
- Pharmaceutical Vehicles
- Acetylmuramyl-Alanyl-Isoglutamine
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Topics |
- Acetylmuramyl-Alanyl-Isoglutamine
(analogs & derivatives, pharmacology)
- Adjuvants, Immunologic
(pharmacology, toxicity)
- Animals
- Antibody Formation
(drug effects)
- Emulsions
- Female
- Fever
(chemically induced)
- Guinea Pigs
- Immunity, Cellular
(drug effects)
- Liposomes
(administration & dosage)
- Pharmaceutical Vehicles
- Rabbits
- Structure-Activity Relationship
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