Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.

Department of Chemistry & Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208, USA.
Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.
Mesh Terms:
Arthritis, Rheumatoid, Chlortetracycline, Combinatorial Chemistry Techniques, Enzyme Inhibitors, Fluorescent Dyes, Hydrolases, Minocycline, Models, Biological, Molecular Structure, Streptomycin, Tetracycline
Bioorg. Med. Chem. Jan. 15, 2008; 16(2);739-45 [PUBMED:17964793]
188476
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