Enhancement of nonspecific resistance to microbial infections of synthetic lipid A-subunit analogues of GLA-27 modified at the C1 position of the glucosamine backbone.
The C1 position of lipid A-subunit analogue GLA-27, 4-O-phosphono-D-glucosamine carrying N-3-tetradecanoyloxytetradecanoyl(C14-O-(C14)) and 3-O-tetradecanoyl (C14) groups, was S-acetylated, thiolated or phosphorylated. Enhancement of nonspecific resistance to Pseudomonas aeruginosa and vaccinia virus infections of these chemically modified compounds were investigated. Thiolation augmented the nonspecific resistance to P. aeruginosa infection. Protective activity against vaccinia virus infection was reduced by all the chemical modifications. NK cell activity was found not to be effected by S-acetylation, but to be decreased slightly by thiolation or phosphorylation. IFN-inducing activity was reduced remarkably by thiolation or S-acetylation, or completely diminished by phosphorylation, compared with that of GLA-27.
Boehringer Mannheim Toho, Kyoto, Japan.
M
M
Nakatsuka
S
S
Ikeda
Y
Y
Kumazawa
M
M
Matsuura
C
C
Nishimura
J Y
JY
Homma
M
M
Kiso
A
A
Hasegawa
D000818:Animals; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007372:Interferons / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000276:immunology*; D013329:Structure-Activity Relationship; D014615:Vaccinia / Q000276:immunology*
D008050:Lipid A; C048988:GLA 27; D007372:Interferons