Abstract
Protein Arginine Deiminase (PAD) activity is dysregulated in numerous diseases, e.g., Rheumatoid Arthritis. Herein we describe the development of a fluorescence polarization-Activity Based Protein Profiling (fluopol-ABPP) based high throughput screening assay that can be used to identify PAD-selective inhibitors. Using this assay, streptonigrin was identified as a potent, selective, and irreversible PAD4 inactivator.
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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Cell Line, Tumor
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Drug Evaluation, Preclinical / methods
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Fluorescence Polarization / methods
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Fluorescent Dyes / chemistry
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High-Throughput Screening Assays / methods*
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Humans
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Hydrolases / antagonists & inhibitors*
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Hydrolases / metabolism*
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Inhibitory Concentration 50
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Protein-Arginine Deiminases
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Streptonigrin / pharmacology
Substances
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Enzyme Inhibitors
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Fluorescent Dyes
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Streptonigrin
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Hydrolases
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Protein-Arginine Deiminases