Abstract
The metabolically stabilized LPA analogue, 1-oleoyl-2-O-methyl-rac-glycerophosphothioate (OMPT), is a potent agonist for the LPA(3) G-protein-coupled receptor. A new enantiospecific synthesis of both (2R)-OMPT and (2S)-OMPT is described. Calcium release assays in both LPA(3)-transfected insect Sf9 and rat hepatoma Rh7777 cells showed that (2S)-OMPT was 5- to 20-fold more active than (2R)-OMPT. Similar results were found for calcium release, MAPK and Akt activation, and IL-6 release in human OVCAR3 ovarian cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Calcium / metabolism
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Cell Line
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Cell Line, Tumor
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Enzyme Activation
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Humans
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Interleukin-6 / biosynthesis
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Lysophospholipids / chemical synthesis*
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Lysophospholipids / chemistry
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Lysophospholipids / pharmacology
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Organothiophosphorus Compounds / chemical synthesis*
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Organothiophosphorus Compounds / chemistry
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Organothiophosphorus Compounds / pharmacology
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Phosphatidic Acids / chemical synthesis*
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Phosphatidic Acids / chemistry
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Phosphatidic Acids / pharmacology
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Receptors, G-Protein-Coupled / agonists*
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Receptors, Lysophosphatidic Acid
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Stereoisomerism
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Structure-Activity Relationship
Substances
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1-oleoyl-2-O-methylglycerophosphothioate
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Interleukin-6
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Lysophospholipids
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Organothiophosphorus Compounds
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Phosphatidic Acids
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Proto-Oncogene Proteins
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Receptors, G-Protein-Coupled
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Receptors, Lysophosphatidic Acid
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AKT1 protein, human
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinase Kinases
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Calcium