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

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    Authors
    Knuckley, Bryan
    Luo, Yuan
    Thompson, Paul R
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2008-01-15
    Keywords
    Arthritis, Rheumatoid
    Chlortetracycline
    Combinatorial Chemistry Techniques
    Enzyme Inhibitors
    Fluorescent Dyes
    Hydrolases
    Minocycline
    Models, Biological
    Molecular Structure
    Streptomycin
    Tetracycline
    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
    Biochemistry
    Enzymes and Coenzymes
    Medicinal-Pharmaceutical Chemistry
    Therapeutics
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267747/
    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.
    Source
    Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Link to article on publisher's site. Epub 2007 Oct 13.
    DOI
    10.1016/j.bmc.2007.10.021
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/50065
    Notes

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

    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.bmc.2007.10.021
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