Synthesis and TNF-alpha inducing activities of mycoloyl-arabinan motif of mycobacterial cell wall components.
The extract of the cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) from Mycobacterium bovis is known to be an activator of innate immunity. Synthesis of pentaarabinofuranoside as part of the arabinan moiety of BCG-CWS was achieved by double alpha-arabinofuranosylation followed by double beta-arabinofuranosylation with orthogonally protected donors. Mycolic esters of the arabinan in the terminal lipo-arabinan motif of BCG-CWS were synthesized through alkylation of unprotected mycolic acid with bis- and tetra-tosylates of pentaarabinofuranoside. A series of compounds were subjected to a tumor necrosis factor alpha (TNF-alpha) secretion-inducing assay, disclosing aspects of the structure-activity relationship which should be useful in finding the site of the activity.
Ishiwata
Akihiro
A
RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Akao
Hiroko
H
Ito
Yukishige
Y
Sunagawa
Makoto
M
Kusunose
Naoto
N
Kashiwazaki
Yasuo
Y
D000818:Animals; D002236:Carbohydrate Conformation; D002460:Cell Line; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism*; D004951:Esterification; D013058:Mass Spectrometry; D051379:Mice; D009163:Mycobacterium bovis / Q000737:chemistry* / Q000378:metabolism*; D009171:Mycolic Acids / Q000737:chemistry; D011134:Polysaccharides / Q000096:biosynthesis* / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D009171:Mycolic Acids; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; C030080:araban