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A detailed kinetic analysis of inactivation by these covalent inhibitors reveals that this class of compounds inhibits a panel of protein tyrosine phosphatases in a time\u2010 and dose\u2010dependent manner, consistent with the covalent modification of the enzyme active site. An inactivation experiment in the presence of sodium arsenate, a known competitive inhibitor of protein tyrosine phosphatase, indicated that these inhibitors were active site bound. This finding is consistent with the mass spectrometric analysis of the covalently modified protein tyrosine phosphatase enzyme. Additional experiments indicated that these compounds remained inert toward other classes of arylphosphate\u2010hydrolyzing enzymes, and alkaline and acid phosphatases. Cell\u2010based experiments with human A549 lung cancer cell lines indicated that 2\u2010(phenylsulfonyl)oxirane (<jats:bold>1<\/jats:bold>) caused an increase in intracellular pTyr levels in a dose\u2010dependent manner thereby suggesting its cell\u2010permeable nature. Taken together, the newly identified 2\u2010(arylsulfonyl)oxiranyl moiety could serve as a novel chemotype for the development of activity\u2010based probes and therapeutic agents against protein tyrosine phosphatase superfamily of enzymes.<\/jats:p>","DOI":"10.1111\/j.1747-0285.2012.01437.x","type":"journal-article","created":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T23:54:37Z","timestamp":1340322877000},"page":"489-499","source":"Crossref","is-referenced-by-count":5,"title":["Design, Synthesis, and Evaluation of 2\u2010(arylsulfonyl)oxiranes as Cell\u2010permeable Covalent Inhibitors of Protein Tyrosine Phosphatases"],"prefix":"10.1111","volume":"80","author":[{"given":"Dibyendu","family":"Dana","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tirtha 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