Dreyton, Christina J.Anderson, Erin D.Subramanian, VenkataramanBoger, Dale L.Thompson, Paul R2022-08-232022-08-232014-02-152015-05-22Bioorg Med Chem. 2014 Feb 15;22(4):1362-9. doi: 10.1016/j.bmc.2013.12.064. Epub 2014 Jan 8. <a href="http://dx.doi.org/10.1016/j.bmc.2013.12.064">Link to article on publisher's site</a>0968-0896 (Linking)10.1016/j.bmc.2013.12.064https://hdl.handle.net/20.500.14038/50009<p>At the time of publication, Christina Dreyton and Paul Thompson were not yet affiliated with UMass Medical School.</p>Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity and human disease, we initiated a program to develop PAD inhibitors as potential therapeutics for these and other diseases in which the PADs are thought to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial activity was later identified as a highly potent PAD4 inhibitor. In an effort to understand why streptonigrin is such a potent and selective PAD4 inhibitor, we explored its structure-activity relationships by examining the inhibitory effects of several analogues that mimic the A, B, C, and/or D rings of streptonigrin. We report the identification of the 7-amino-quinoline-5,8-dione core of streptonigrin as a highly potent pharmacophore that acts as a pan-PAD inhibitor.en-USAnimalsAntineoplastic AgentsCell LineCell ProliferationCell SurvivalEnzyme InhibitorsHumansHydrolasesKineticsMiceProtein BindingProtein IsoformsQuinolinesStreptonigrinStructure-Activity RelationshipBiochemistryEnzymes and CoenzymesMedicinal-Pharmaceutical ChemistryTherapeuticsJournal Articlehttps://escholarship.umassmed.edu/thompson/207135670thompson/20