title: A fluopol-ABPP HTS assay to identify PAD inhibitors.
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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Scripps Florida, 120 Scripps Way, Jupiter, Florida, USA33458.
authors.forename: Bryan
authors.initials: B
authors.lastname: Knuckley
authors.forename: Justin E
authors.initials: JE
authors.lastname: Jones
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bachovchin
authors.forename: Jessica
authors.initials: J
authors.lastname: Slack
authors.forename: Corey P
authors.initials: CP
authors.lastname: Causey
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Brown
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Cravatt
authors.forename: Paul R
authors.initials: PR
authors.lastname: Thompson
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005454:Fluorescence Polarization / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D000076342:Protein-Arginine Deiminases; D013308:Streptonigrin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D013308:Streptonigrin; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases