Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / enzymology
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Chlortetracycline / pharmacology
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Combinatorial Chemistry Techniques
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Fluorescent Dyes / chemical synthesis*
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Fluorescent Dyes / pharmacology
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Hydrolases / antagonists & inhibitors*
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Minocycline / pharmacology
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Models, Biological
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Molecular Structure
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Protein-Arginine Deiminase Type 4
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Protein-Arginine Deiminases
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Streptomycin / pharmacology
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Tetracycline / pharmacology
Substances
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Enzyme Inhibitors
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Fluorescent Dyes
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Hydrolases
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Protein-Arginine Deiminase Type 4
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Protein-Arginine Deiminases
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Tetracycline
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Minocycline
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Chlortetracycline
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Streptomycin