Stereochemical properties of lysophosphatidic acid receptor activation and metabolism
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. © 2002 Elsevier Science B.V. All rights reserved.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Yokoyama, K., Baker, D., Virag, T., Liliom, K., Byun, H., Tigyi, G., & Bittman, R. (2002). Stereochemical properties of lysophosphatidic acid receptor activation and metabolism. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1582 (2022-01-03), 295-308. https://doi.org/10.1016/S1388-1981(02)00184-1