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.

Herein we describe a novel screen for PAD4 inhibitors that is based on an Activity-Based Protein Profiling Reagent that covalently modifies PAD4 and renders it fluorescent.Figure optionsDownload as PowerPoint slide