Phosphatidylinositol mannosides: Synthesis and adjuvant properties of phosphatidylinositol di- and tetramannosides

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 22; pp. 7615 - 7624
• Main Authors: Ainge, Gary D., Parlane, Natalie A., Denis, Michel, Hayman, Colin M., Larsen, David S., Painter, Gavin F.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.11.2006; Elsevier Science
• Subjects: Adjuvant; Adjuvants, Immunologic - chemical synthesis; Adjuvants, Immunologic - chemistry; Animals; Biological and medical sciences; Carbohydrate Conformation; Immunomodulation; Immunomodulators; Mannosides - chemical synthesis; Mannosides - chemistry; Mannosides - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Ovalbumin - immunology; Pharmacology. Drug treatments; Phosphatidylinositol mannosides; Phosphatidylinositols - chemical synthesis; Phosphatidylinositols - chemistry; Phosphatidylinositols - immunology; Synthesis; Adjuvant; Synthesis; Phosphatidylinositol mannosides; Immunomodulation; Transgenic animal; Phospholipid; Selectivity; Disaccharide; Phosphatidylinositol; Chemical synthesis; Diol; Rodentia; Cytokine; Glycosylation; Complex lipid; Biological activity; Glycolipid; Antigen; Immunomodulator; Vertebrata; Mammalia; Mouse; Models; Tetrasaccharide; Gamma interferon
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.07.003

The adjuvant properties of synthetic phosphatidylinositol mannosides PIM2 1 and PIM4 2 were tested in an in vivo mouse model. Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of glycolipids with significant immune modulating properties. We present here the syntheses of phosphatidylinositol dimannoside (PIM2, 1) and phosphatidylinositol tetramannoside (PIM4, 2) and evaluate their adjuvant properties in a transgenic mouse model. The key step in the synthetic methodology for the synthesis of 2 relies on the selective glycosylation of diol 3 with mannosyl donor 11. Both synthetic PIMs were effective at enhancing IFN-γ when given as adjuvants with a model antigen, with PIM2 being the more active. These data suggest that in this assay the PIM core structure is responsible for the observed biological activity.