Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Arthritis, Rheumatoid; Chlortetracycline; Combinatorial Chemistry Techniques; Enzyme Inhibitors; Fluorescent Dyes; Hydrolases; Minocycline; Models, Biological; Molecular Structure; Streptomycin; Tetracycline
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
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.
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Citation: Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Link to article on publisher's site. Epub 2007 Oct 13.
Protein Arginine Deiminase 4, Minocycline, Streptomycin, Chlortetracycline, Tetracycline, Rheumatoid Arthritis, DMARD, arginine, Assay, Screen, Arginine deiminase, Inhibitor, Rhodamine, F-amidine, Fluoro, RFA, Activity-Based Protein Profiling, ABPP
Knuckley, Bryan; Luo, Yuan; and Thompson, Paul R., "Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors" (2008). Thompson Lab Publications. 71.