title: Phosphatidylinositol mannosides: synthesis and adjuvant properties of phosphatidylinositol di- and tetramannosides.
abstract: 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-gamma 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.
authors.affiliation: Carbohydrate Chemistry Team, Industrial Research Limited, Lower Hutt, New Zealand.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Ainge
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Parlane
authors.forename: Michel
authors.initials: M
authors.lastname: Denis
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D002236:Carbohydrate Conformation; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010716:Phosphatidylinositols / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D008362:Mannosides; D010716:Phosphatidylinositols; C054977:phosphatidylinositol dimannoside; D010047:Ovalbumin