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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anilides / chemical synthesis
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Anilides / chemistry*
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Anilides / pharmacology
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Antitubercular Agents / chemical synthesis
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Antitubercular Agents / chemistry*
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Antitubercular Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Humans
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / enzymology*
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
Substances
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Anilides
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Antitubercular Agents
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Bacterial Proteins
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Enzyme Inhibitors
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MptpA protein, Mycobacterium tuberculosis
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benzanilide
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Protein Tyrosine Phosphatases