Synthesis, pharmacology, and cell biology of sn-2-aminooxy analogues of lysophosphatidic acid.
An efficient enantioselective synthesis of sn-2-aminooxy (AO) analogues of lysophosphatidic acid (LPA) that possess palmitoyl and oleoyl acyl chains is presented. Both sn-2-AO LPA analogues are agonists for the LPA1, LPA2, and LPA4 G-protein-coupled receptors, but antagonists for the LPA3 receptor and inhibitors of autotaxin (ATX). Moreover, both analogues stimulate migration of intestinal epithelial cells in a scratch wound assay.
Gajewiak
Joanna
J
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Salt Lake City, UT 84108-1257, USA.
Tsukahara
Ryoko
R
Fujiwara
Yuko
Y
Tigyi
Gabor
G
Prestwich
Glenn D
GD
D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D008246:Lysophospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors; D000099189:Lysophospholipase D
D008246:Lysophospholipids; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid