Abstract
[reaction: see text] The susceptibility of lysophosphatidic acid (LPA) to intramolecular acyl migration impedes the determination of specific receptor activation by the sn-1 and sn-2 LPA regioisomers. An efficient enantioselective synthesis of hydroxyethoxy (HE)-substituted analogues of sn-1-acyl and 2-acyl LPA derivatives that possess palmitoyl and oleoyl chains is described. While the palmitoyl derivatives fail to activate calcium release in cells transfected with LPA(2) or LPA(3) G-protein-coupled receptors, the LPA(3) receptor is activated by both 1-HE and 2-HE oleoyl LPA analogues with a potency 10-fold lower than that of the parent oleoyl LPA.
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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Acylation
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Animals
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Calcium / metabolism
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Calcium Signaling / drug effects
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Cell Line, Tumor
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Cell Movement / drug effects
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Isomerism
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Lysophospholipids / chemical synthesis*
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Lysophospholipids / chemistry*
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Lysophospholipids / pharmacology
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Molecular Structure
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Rats
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, G-Protein-Coupled / agonists
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Receptors, Lysophosphatidic Acid
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Transcription Factors / metabolism
Substances
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Lysophospholipids
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Receptors, Cytoplasmic and Nuclear
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Receptors, G-Protein-Coupled
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Receptors, Lysophosphatidic Acid
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Transcription Factors
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Calcium