Title
Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
1-15-2008
Document Type
Article
Subjects
Arthritis, Rheumatoid; Chlortetracycline; Combinatorial Chemistry Techniques; Enzyme Inhibitors; Fluorescent Dyes; Hydrolases; Minocycline; Models, Biological; Molecular Structure; Streptomycin; Tetracycline
Disciplines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
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.
Keywords
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
10.1016/j.bmc.2007.10.021
Source
Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Link to article on publisher's site. Epub 2007 Oct 13.
Journal/Book/Conference Title
Bioorganic and medicinal chemistry
Related Resources
Repository Citation
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.
https://escholarship.umassmed.edu/thompson/71
Comments
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.