title: Molecular basis for lysophosphatidic acid receptor antagonist selectivity.
abstract: Recent characterization of lysophosphatidic acid (LPA) receptors has made possible studies elucidating the structure-activity relationships (SAR) for agonist activity at individual receptors. Additionally, the availability of these receptors has allowed the identification of antagonists of LPA-induced effects. Two receptor-subtype selective LPA receptor antagonists, one selective for the LPA1/EDG2 receptor (a benzyl-4-oxybenzyl N-acyl ethanolamide phosphate, NAEPA, derivative) and the other selective for the LPA3/EDG7 receptor (diacylglycerol pyrophosphate, DGPP, 8:0), have recently been reported. The receptor SAR for both agonists and antagonists are reviewed, and the molecular basis for the difference between agonism and antagonism as well as for receptor-subtype antagonist selectivity identified by molecular modeling is described. The implications of the newly available receptor-subtype selective antagonists are also discussed.
authors.affiliation: Department of Chemistry and Computational Research on Materials Institute, The University of Memphis, Memphis, TN 38152-6060, USA.
authors.forename: Vineet M
authors.initials: VM
authors.lastname: Sardar
authors.forename: Debra L
authors.initials: DL
authors.lastname: Bautista
authors.forename: David J
authors.initials: DJ
authors.lastname: Fischer
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Nora
authors.initials: N
authors.lastname: Nusser
authors.forename: Tamas
authors.initials: T
authors.lastname: Virag
authors.forename: De-an
authors.initials: DA
authors.lastname: Wang
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Baker
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.forename: Abby L
authors.initials: AL
authors.lastname: Parrill
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D010743:Phospholipids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid