title: Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA.
abstract: The development of low muM inhibitors of the Mycobacterium tuberculosis phosphatase PtpA is reported. The most potent of these inhibitors (K(i)=1.4+/-0.3 microM) was found to be selective when tested against a panel of human tyrosine and dual-specificity phosphatases (11-fold vs the highly homologous HCPtpA, and >70-fold vs all others tested). Modeling the inhibitor-PtpA complexes explained the structure-activity relationships observed in vitro and revealed further possibilities for compound development.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720 1460, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Rawls
authors.forename: P Therese
authors.initials: PT
authors.lastname: Lang
authors.forename: Jun
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Imamura
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Baguley
authors.forename: Christoph
authors.initials: C
authors.lastname: Grundner
authors.forename: Tom
authors.initials: T
authors.lastname: Alber
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Ellman
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
chemical_list: D000813:Anilides; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C414465:MptpA protein, Mycobacterium tuberculosis; C034595:benzanilide; D017027:Protein Tyrosine Phosphatases