Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.
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.
Knuckley
Bryan
B
Department of Chemistry & Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208, USA.
Luo
Yuan
Y
Thompson
Paul R
PR
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000201:enzymology; D002751:Chlortetracycline / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D008911:Minocycline / Q000494:pharmacology; D008954:Models, Biological; D015394:Molecular Structure; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013307:Streptomycin / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013752:Tetracycline; D008911:Minocycline; D002751:Chlortetracycline; D013307:Streptomycin