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Physicochemical and biological characterization of synthetic phosphatidylinositol dimannosides and analogues.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2013 May 06; Vol. 10 (5), pp. 1928-39. Date of Electronic Publication: 2013 Mar 25. - Publication Year :
- 2013
-
Abstract
- Native phosphatidylinositol mannosides (PIMs), isolated from the cell wall of Mycobacterium bovis, and synthetic PIM analogues have been reported to offer a variety of immunomodulating properties, including both suppressive and stimulatory activity. While numerous studies have examined the biological activity of these molecules, the aim of this research was to assess the physicochemical properties at a molecular level and correlate these characteristics with biological activity in a mouse model of airway eosinophilia. To accomplish this, we varied the flexibility and lipophilicity of synthetic PIMs by changing the polar headgroup (inositol- vs glycerol-based core) and the length of the acyl chains of the fatty acid residues (C0, C10, C16, and C18). A series of six phosphatidylinositol dimannosides (PIM2s) and phosphatidylglycerol dimannosides (PGM2s) were synthesized and characterized in this study. Langmuir monolayer studies showed that surface pressure-area (π-A) isotherms were greatly influenced by the length of the lipid acyl chains as well as the steric hindrance and volume of the headgroups. In aqueous solution, lipidated PIM2 and PGM2 compounds were observed to self-assemble into circular aggregates, as confirmed by dynamic light scattering and transmission electron microscopic investigations. Removal of the inositol ring but retention of the three-carbon glycerol unit maintained biological activity. We found that the deacylated PGM2, which did not show self-organization, had no effect on the eosinophil numbers but did have an impact on the expansion of OVA-specific CD4(+) Vα2Vβ5 T cells.
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
Cell Wall chemistry
Cell Wall immunology
Chemical Phenomena
Cytokines biosynthesis
Disease Models, Animal
Immunologic Factors chemical synthesis
Immunologic Factors chemistry
Immunologic Factors pharmacology
Male
Mannosides pharmacology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Electron, Transmission
Molecular Structure
Mycobacterium bovis chemistry
Mycobacterium bovis immunology
Ovalbumin immunology
Particle Size
Phosphatidylinositols pharmacology
Pulmonary Eosinophilia immunology
Pulmonary Eosinophilia prevention & control
Mannosides chemistry
Mannosides immunology
Phosphatidylinositols chemistry
Phosphatidylinositols immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 23469864
- Full Text :
- https://doi.org/10.1021/mp300707a