Activity-based protein profiling reagents for protein arginine deiminase 4 (PAD4): synthesis and in vitro evaluation of a fluorescently labeled probe

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Fluorescent Dyes; Hydrolases; In Vitro Techniques


Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


Protein arginine deiminase 4 (PAD4), which catalyzes the post-translational conversion of peptidyl arginine to peptidyl citrulline, is widely regarded as one of the best new targets for the development of a novel rheumatoid arthritis therapeutic. In addition to its presumed role in this disease, PAD4 is also a calcium-dependent histone deiminase that acts as a transcriptional co-repressor. Herein we describe the design, synthesis, and in vitro evaluation of two fluorescently labeled activity-based protein profiling (ABPP) reagents that specifically and irreversibly modify the active, that is, calcium-bound, form PAD4 with equal affinity to previously described small molecule chemical probes of PAD4 function. These fluorescently tagged ABPPs will be useful for identifying the conditions under which this enzyme is activated in vivo and may prove to be useful RA diagnostics.

DOI of Published Version



J Am Chem Soc. 2006 Nov 15;128(45):14468-9. Link to article on publisher's site

Journal/Book/Conference Title

Journal of the American Chemical Society


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed