Synthesis and TNF-α 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 α-arabinofuranosylation followed by double β-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-α) secretion-inducing assay, disclosing aspects of the structure–activity relationship which should be useful in finding the site of the activity.

The aim of this study was to synthesize a series of mono- (1), di- (2, 3, 4) and tetramycolated (5) arabinans, which constitute the terminal region of BCG-CWS. In addition, their activities to induce TNF-α were evaluated.Figure optionsDownload as PowerPoint slide