Title

Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

1-15-2008

Document Type

Article

Medical Subject Headings

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.

Rights and Permissions

Citation: Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Link to article on publisher's site. Epub 2007 Oct 13.

Comments

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed

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