Phosphorothioate analogs of sn-2 radyl lysophosphatidic acid (LPA): Metabolically stabilized LPA receptor agonists

Guowei Jiang, Asuka Inoue, Junken Aoki, Glenn D. Prestwich

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We describe an efficient synthesis of metabolically stabilized sn-2 radyl phosphorothioate analogs of lysophosphatidic acid (LPA), and the determination of the agonist activity of each analog for the six LPA receptors (LPA 1-6) using a recently developed TGFα shedding assay. In general, the sn-2 radyl OMPT analogs showed similar agonist activities to the previous 1-oleoyl-2-O-methyl-glycerophosphothioate (sn-1 OMPT) analogs for LPA1-6 receptors. In most cases, the sn-2 radyl-OMPT analogs were more potent agonists than LPA itself. Most importantly, sn-2 alkyl OMPT analogs were very potent LPA5 and LPA6 agonists. The availability of sn-2 radyl OPMT analogs further refines the structure-activity relationships for ligand-receptor interactions for this class of GPCRs.

Original languageEnglish
Pages (from-to)1865-1869
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number6
DOIs
Publication statusPublished - 2013 Mar 15

Keywords

  • Agonist
  • Lysophosphatidic acid
  • Structure-activity relationship
  • Transforming growth factor-(TGFα) shedding assay
  • sn-2 Radyl phosphorothioate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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