Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors
Department of Biochemistry and Molecular Pharmacology
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.
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
DOI of Published Version
Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Link to article on publisher's site. Epub 2007 Oct 13.
Bioorganic and medicinal chemistry
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.