Synthesis and TNF-α inducing activities of mycoloyl-arabinan motif of mycobacterial cell wall components
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. The extract of the cell wall skeleton of Bacillus Calmette–Guérin (BCG-CWS)...
Gespeichert in:
Veröffentlicht in: | Bioorganic & medicinal chemistry 2006-05, Vol.14 (9), p.3049-3061 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | 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.
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. |
---|---|
ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2005.12.037 |