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Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
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PAD2 Activity Monitored via a Fluorescent Substrate Analog.

Mary J Sabulski1, Yanming Wang2, Marcos M Pires1

  • 1Chemistry Department, Lehigh University, Bethlehem, PA, 18015, USA.

Chemical Biology & Drug Design
|February 4, 2015
PubMed
Summary

We developed a novel profluorescent assay to monitor peptidyl arginine deiminase 2 (PAD2) activity and inhibition. This tool aids in understanding PAD2

Keywords:
PAD2PAD4citrullinationfluorescence assayinhibitor

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Area of Science:

  • Biochemistry
  • Enzymology
  • Chemical Biology

Background:

  • Peptidyl arginine deiminase 2 (PAD2) catalyzes the conversion of arginine to citrulline, a post-translational modification impacting protein properties.
  • Dysregulated PAD2 activity is linked to various human diseases, highlighting its potential as a therapeutic target.
  • Small molecule inhibitors of PAD2 are crucial for probing its role in disease pathogenesis.

Purpose of the Study:

  • To develop a robust assay for monitoring PAD2 activity.
  • To create a tool for screening PAD2 inhibitors.
  • To facilitate drug discovery efforts targeting PAD2.

Main Methods:

  • Design and synthesis of a profluorescent substrate analog for PAD2.
  • Establishment of a robust assay to detect PAD2 activity and inhibition.
  • Characterization of the assay's performance and utility.

Main Results:

  • A novel profluorescent substrate analog was successfully developed.
  • The assay effectively reports on PAD2 activity.
  • The assay demonstrates utility in monitoring PAD2 inhibition by small molecules.

Conclusions:

  • The developed profluorescent assay provides a valuable tool for studying PAD2.
  • This assay is suitable for drug discovery efforts aimed at inhibiting PAD2.
  • Future research can leverage this assay to explore PAD2's role in disease and develop new therapeutics.