Development of an Activity-Based Probe for Autotaxin

Silvia Cavalli, Anna J.S. Houben, Harald M.H.G. Albers, Erica W. Van Tilburg, Arnoud De Ru, Junken Aoki, Peter Van Veelen, Wouter H. Moolenaar, Huib Ovaa

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Autotaxin (ATX), or ecto-nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), is a secreted lysophospholipase D that hydrolyses lysophosphatidylcholine into the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX has been implicated in tumour progression and inflammation, and might serve as a biomarker. Here we describe the development of a fluorescent activity-based probe that covalently binds to the active site of ATX. The probe consists of a lysophospholipid-based backbone linked to a trapping moiety that becomes reactive after phosphate ester hydrolysis, and a Cy5 fluorescent dye to allow visualisation of active ATX. The probe reacts specifically with the three known isoforms of ATX, it competes with small-molecule inhibitors for binding to ATX and allows ATX activity in plasma to be determined. Our activity-based reporter will be useful for monitoring ATX activity in biological fluids and for inhibitor screening.Marking biomarkers: ATX is a secreted lysophospholipase D that produces the lipid mediator lysophosphatidic acid. We have developed a fluorescent activity-based probe that covalently binds to the active site of ATX, allowing visualisation of active ATX. This probe can be used for monitoring ATX activity in body fluids and for inhibitor screening.

Original languageEnglish
Pages (from-to)2311-2317
Number of pages7
JournalChemBioChem
Volume11
Issue number16
DOIs
Publication statusPublished - 2010 Nov 2

Keywords

  • Autotaxin
  • Biomarkers
  • Enzymes
  • Inhibitors
  • Lysophospholipase D

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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