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Related Experiment Videos

Fluorogenic phospholipid substrate to detect lysophospholipase D/autotaxin activity.

Colin G Ferguson1, Cleve S Bigman, Robyn D Richardson

  • 1Echelon Biosciences Inc., Salt Lake City, Utah 84108, USA. cferguson@echelon-inc.com

Organic Letters
|May 5, 2006
PubMed
Summary

Researchers developed novel fluorogenic substrates to detect lysophospholipase D (lysoPLD), also known as autotaxin (ATX). These tools aid in screening for ATX, a key enzyme in producing the mitogen lysophosphatidic acid (LPA).

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Area of Science:

  • Biochemistry
  • Enzymology
  • Drug Discovery

Background:

  • Lysophospholipase D (lysoPLD), also known as autotaxin (ATX), generates lysophosphatidic acid (LPA), a significant mitogen.
  • ATX is an emerging drug target due to its role in various physiological and pathological processes.

Purpose of the Study:

  • To synthesize novel fluorogenic substrate analogues for the detection and screening of lysoPLD/ATX activity.
  • To evaluate the utility of these substrates in identifying potential inhibitors of ATX.

Main Methods:

  • Two fluorogenic substrate analogues, FS-2 and FS-3, were synthesized.
  • The synthesis involved a nine-step process starting from (S)-PMB-glycerol.
  • Recombinant ATX was used to test the substrates' responsiveness.

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Main Results:

  • The synthesized substrates (FS-2 and FS-3) exhibited significant increases in fluorescence upon incubation with recombinant ATX.
  • The substrates demonstrated high sensitivity to ATX enzymatic activity.

Conclusions:

  • Novel fluorogenic substrates for lysoPLD/ATX have been successfully synthesized.
  • These substrates are valuable tools for high-throughput screening assays targeting ATX.
  • The development facilitates the discovery of new therapeutic agents targeting ATX-related diseases.