Abstract
An unprecedented phosphatidylmonogalactosyldiacylglycerol pool (PGDG, 1) rich in polyunsaturated fatty acids was isolated from the marine diatoms Thalassiosira weissflogii. Here we report for the first time the NMR characterization of this rare lipid from marine organisms along with a synthetic strategy for the preparation of a PGDG analog (2). PGDG 1 exhibited immunostimulatory activity in human dendritic cells (DCs) and the synthetic PGDG 2 was prepared to explore its mechanism of action. A Toll-like receptor-4 (TLR-4) agonistic activity was evidenced in human and murine DCs underlying the antigen-specific T-cell activation of this class of molecules.
Keywords:
Thalassiosira weissflogii; Toll-like receptor 4; dendritic cells; immunostimulatory lipid; marine diatom; phosphogalactolipids; phosphoglycolipid synthesis.
MeSH terms
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Adjuvants, Immunologic / chemical synthesis
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Adjuvants, Immunologic / chemistry*
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Adjuvants, Immunologic / isolation & purification
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Adjuvants, Immunologic / pharmacology*
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Animals
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Carbon-13 Magnetic Resonance Spectroscopy
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Cells, Cultured
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Diatoms / chemistry*
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Female
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Glycolipids / chemical synthesis
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Glycolipids / chemistry*
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Glycolipids / isolation & purification
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Glycolipids / pharmacology*
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Humans
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Phosphatidylglycerols / chemical synthesis
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Phosphatidylglycerols / chemistry*
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Phosphatidylglycerols / isolation & purification
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Phosphatidylglycerols / pharmacology*
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Toll-Like Receptor 4 / agonists*
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Toll-Like Receptor 4 / immunology
Substances
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Adjuvants, Immunologic
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Glycolipids
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Phosphatidylglycerols
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TLR4 protein, human
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Toll-Like Receptor 4
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phosphatidylmonoglycosyl diacylglycerol