Stereochemical properties of lysophosphatidic acid receptor activation and metabolism

Kazuaki Yokoyama, Daniel L. Baker, Tamas Virag, K. Liliom, Hoe Sup Byun, Gabor Tigyi, Robert Bittman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Ligand recognition by G protein-coupled receptors (GPCR), as well as substrate recognition by enzymes, almost always shows a preference for a naturally occurring enantiomer over the unnatural one. Recognition of lysophosphatidic acid (LPA) by its receptors is an exception, as both the natural L (R) and unnatural D (S) stereoisomers of LPA are equally active in bioassays. In contrast to the enantiomers of LPA, analogs of N-acyl-serine phosphoric acid (NASPA) and N-acyl-ethanolamine phosphoric acid (NAEPA), which contain a serine and an ethanolamine backbone, respectively, in place of glycerol, are recognized in a stereoselective manner. This stereoselective interaction may lead to the development of receptor subtype-selective antagonists. In the present study, we review the stereochemical aspects of LPA pharmacology and describe the chemical synthesis of pure LPA enantiomers together with their ligand-binding properties toward the LPA1, LPA2, and LPA3 receptors and their metabolism by lipid phosphate phosphatase 1 (LPP1). Finally, we evaluate the concept of stereopharmacology in developing novel ligands for LPA receptors.

Original languageEnglish
Pages (from-to)295-308
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1582
Issue number1-3
DOIs
Publication statusPublished - May 23 2002

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Lysophosphatidic Acid Receptors
Ethanolamine
Ligands
Serine
Stereoisomerism
G-Protein-Coupled Receptors
Biological Assay
Glycerol
Pharmacology
lysophosphatidic acid
Enzymes

Keywords

  • Lipid phosphate phosphatase 1
  • Lipid synthesis
  • LPA antagonist
  • LPA receptor
  • Stereoselectivity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

Cite this

Stereochemical properties of lysophosphatidic acid receptor activation and metabolism. / Yokoyama, Kazuaki; Baker, Daniel L.; Virag, Tamas; Liliom, K.; Byun, Hoe Sup; Tigyi, Gabor; Bittman, Robert.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1582, No. 1-3, 23.05.2002, p. 295-308.

Research output: Contribution to journalArticle

Yokoyama, Kazuaki ; Baker, Daniel L. ; Virag, Tamas ; Liliom, K. ; Byun, Hoe Sup ; Tigyi, Gabor ; Bittman, Robert. / Stereochemical properties of lysophosphatidic acid receptor activation and metabolism. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2002 ; Vol. 1582, No. 1-3. pp. 295-308.
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