| Title | Chemical synthesis and immunosuppressive activity of dipalmitoyl phosphatidylinositol hexamannoside |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Ainge, G. D., Compton B. J., Hayman C. M., Martin W. J., Toms S. M., Larsen D. S., Harper J. L., and Painter G. F. |
| IRL Team | Carbohydrate Chemistry |
| Journal | Journal of Organic Chemistry |
| Volume | 76 |
| Pagination | 4941-4951 |
| Keywords | article, CD8+ T lymphocyte, Chemical modification, chemical structure, Chemical synthesis, chromatography, Deacylation, dendritic cell, dipalmitoylphosphatidylinositol hexamannoside, esterification, Glycosylation, H NMR spectra, high performance liquid chromatography, human, human cell, immunomodulating agent, immunomodulation, Mixed lymphocyte reaction, Mycobacterium, nonhuman, nuclear magnetic resonance spectroscopy, phosphatidylinositol, proton nuclear magnetic resonance, Reverse phase chromatography, Spectroscopic analysis, Spectroscopic method, Sugars, synthesis, Synthesis (chemical), Synthetic protocols, T cells, unclassified drug |
| 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 (PIM6) 1 and the first reported functional biology of a synthetic PIM6. 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 dPIM6. The 1H NMR[?] spectrum of synthetic dPIM6 obtained from 1 matched that of dPIM6 obtained from nature. PIM6 (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. © 2011 American Chemical Society. |
| URL | http://www.scopus.com/inward/record.url?eid=2-s2.0-79958837488&partnerID=40&md5=9d0be249bce03475f7210fb73213d868 |
| DOI | 10.1021/jo200588u |
