title: Chemical synthesis and immunosuppressive activity of dipalmitoyl phosphatidylinositol hexamannoside.
abstract: Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of phosphoglycolipids with significant immune-modulating properties. We present here the synthesis of dipalmitoyl phosphatidylinositol hexamannoside (PIM(6)) 1 and the first reported functional biology of a synthetic PIM(6). Key steps in the synthetic protocol included the selective glycosylation of an inositol 2,6-diol with a suitably protected mannosyl donor and construction of the glycan core utilizing a [3 + 4] thio-glycosylation strategy. The target 1 was purified by reverse phase chromatography and characterized by standard spectroscopic methods, HPLC, and chemical modification by deacylation to dPIM(6). The (1)H NMR spectrum of synthetic dPIM(6) obtained from 1 matched that of dPIM(6) obtained from nature. PIM(6) (1) exhibited dendritic cell-dependent suppression of CD8(+) T cell expansion in a human mixed lymphocyte reaction consistent with the well established immunosuppressive activity of whole mycobacteria.
authors.affiliation: Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31-310, Lower Hutt, New Zealand.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Ainge
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Compton
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hayman
authors.forename: William John
authors.initials: WJ
authors.lastname: Martin
authors.forename: Steven M
authors.initials: SM
authors.lastname: Toms
authors.forename: David S
authors.initials: DS
authors.lastname: Larsen
authors.forename: Jacquie L
authors.initials: JL
authors.lastname: Harper
authors.forename: Gavin F
authors.initials: GF
authors.lastname: Painter
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D015394:Molecular Structure; D010716:Phosphatidylinositols / Q000138:chemical synthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D010716:Phosphatidylinositols; C560959:dipalmitoyl phosphatidylinositol hexamannoside; C034154:phosphatidylinositol mannoside