Development of an Activity-Based Probe for Autotaxin

被引：10

作者：

Cavalli, Silvia ^{[1
,2
]}

Houben, Anna J. S. ^{[1
]}

Albers, Harald M. H. G. ^{[1
]}

van Tilburg, Erica W. ^{[1
,3
]}

de Ru, Arnoud ^{[4
]}

Aoki, Junken ^{[5
]}

van Veelen, Peter ^{[4
]}

Moolenaar, Wouter H. ^{[1
]}

Ovaa, Huib ^{[1
]}

机构：

[1] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands

[2] Biomed Res Inst, Networking Ctr Bioengn Biomat & Nanomed, CIBER BBN, Barcelona 08028, Spain

[3] Erasmus MC, Dept Nucl Med, NL-3015 CE Rotterdam, Netherlands

[4] Leiden Univ, Med Ctr, Div Immunohematol & Blood Transfus, NL-2333 ZA Leiden, Netherlands

[5] Tohoku Univ, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan

来源：

CHEMBIOCHEM | 2010年 / 11卷 / 16期

关键词：

autotaxin; biomarkers; enzymes; inhibitors; lysophospholipase D; PROTEIN-TYROSINE PHOSPHATASES; LYSOPHOSPHATIDIC ACID; LYSOPHOSPHOLIPASE-D; FLUORESCENT-PROBES; NEUROPATHIC PAIN; ENZYME; LPA; IDENTIFICATION; INHIBITOR; MOTILITY;

D O I：

10.1002/cbic.201000349

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2311 / 2317

页数：7

共 31 条

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