Synthesis, pharmacology, and cell biology of sn-2-aminooxy analogues of lysophosphatidic acid

Org Lett. 2008 Mar 20;10(6):1111-4. doi: 10.1021/ol7030747. Epub 2008 Feb 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cricetinae
  • Cricetulus
  • Lysophospholipids / chemical synthesis*
  • Lysophospholipids / chemistry
  • Lysophospholipids / pharmacology*
  • Molecular Structure
  • Multienzyme Complexes / antagonists & inhibitors
  • Phosphodiesterase I / antagonists & inhibitors
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases / antagonists & inhibitors
  • Rats
  • Receptors, Lysophosphatidic Acid / antagonists & inhibitors

Substances

  • Lysophospholipids
  • Multienzyme Complexes
  • Receptors, Lysophosphatidic Acid
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • Pyrophosphatases
  • lysophosphatidic acid