Abstract
An improved synthesis of two lipid phosphoric acids, N-palmitoyl-L-serine phosphoric acid (NP-Ser-PA) and N-palmitoyl-L-tyrosine phosphoric acid (NP-Tyr-PA), from the benzyl esters of L-serine and L-tyrosine is described. The sequence of N-acylation, followed by phosphitylation with N, N-diisopropyl dibenzyl phosphoramidite, oxidation to the corresponding phosphate triesters, and simultaneous debenzylation of the dibenzyl phosphate and benzyl carboxylic esters gave NP-Ser-PA and NP-Tyr-PA in high overall yields. NP-Ser-PA and NP-Tyr-PA and their D stereoisomers were potent reversible inhibitors of the lysophosphatidic acid receptors expressed in Xenopus oocytes, thus providing prototypic structures for the development of inhibitors of the lysophosphatidate family of phospholipid growth factors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Membrane / physiology
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Chloride Channels / drug effects
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Chloride Channels / physiology
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Electric Conductivity
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Female
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Oocytes / metabolism
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Oocytes / ultrastructure
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Palmitates / chemical synthesis*
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Palmitates / pharmacology
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Phosphoserine / analogs & derivatives*
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Phosphoserine / chemical synthesis
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Phosphoserine / pharmacology
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Phosphotyrosine / analogs & derivatives*
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Phosphotyrosine / chemical synthesis
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Phosphotyrosine / pharmacology
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Receptors, Cell Surface / antagonists & inhibitors*
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Receptors, G-Protein-Coupled*
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Receptors, Lysophosphatidic Acid
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Recombinant Proteins / antagonists & inhibitors
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Stereoisomerism
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Xenopus
Substances
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Chloride Channels
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N-palmitoylserine phosphoric acid
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N-palmitoyltyrosine phosphoric acid
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Palmitates
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Receptors, Lysophosphatidic Acid
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Recombinant Proteins
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Phosphoserine
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Phosphotyrosine