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Dr. Paul Thompson Lab publishes paper in Angewandte Chemie

Date Posted: Monday, August 05, 2019

Halogen Bonding Increases the Potency and Isozyme-selectivity of Protein Arginine Deiminase 1 InhibitorsProtein Arginine Deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known.  In Angewandte Chemie, a premiere chemistry journal, the Thompson lab describes the first potent and isozyme-selective PAD1 inhibitors.  This work, spearheaded by Santanu Mondal, a postdoc in the Thompson lab, is particularly notable because these PAD1 inhibitors contain iodine-substitutions and detailed studies indicate that their potency and isozyme-selectivity is derived from the formation of a halogen bond with PAD1.  These inhibitors exhibit excellent efficiency for the inhibition of histone H3 citrullination in cells and mouse embryos. Based on this inhibitor scaffold, the Thompson lab also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome-wide selectivity.  These compounds will be useful tools to probe the cellular roles of PAD1 and may represent novel therapeutics.


PMID:   31276611
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