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P(450)/NADPH/O(2)- and P(450)/PhIO-catalyzed N-dealkylations are mechanistically distinct

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dc.contributor Wichita State University. Department of Chemistry en_US
dc.contributor.author Bhakta, Mehul N. en_US
dc.contributor.author Hollenberg, Paul F. en_US
dc.contributor.author Wimalasena, Kandatege en_US
dc.date.accessioned 2012-02-06T17:17:08Z
dc.date.available 2012-02-06T17:17:08Z
dc.date.issued 2005-02-09 en_US
dc.identifier 15686361 en_US
dc.identifier 7503056 en_US
dc.identifier CA 16954/ GM 45026 en_US
dc.identifier.citation Journal of the American Chemical Society. 2005 Feb 9; 127(5): 1376-7. en_US
dc.identifier.issn 0002-7863 en_US
dc.identifier.uri http://dx.doi.org/10.1021/ja0436143 en_US
dc.identifier.uri http://hdl.handle.net/10057/4399
dc.description Click on the DOI link below to access the article (may not be free). en_US
dc.description.abstract A high-valent iron-oxo species analogous to the compound I of peroxidases has been thought to be the activated oxygen species in P450-catalyzed reactions. Spectroscopic characterization of the catalytically competent iron-oxo species in iodosobenzene (PhIO)-supported model reactions and parallels between these model reactions and PhIO- and NADPH/O2-supported P450 reactions have been taken as strong evidence for this proposal. To support this proposal, subtle differences observed in regio- and chemoselectivities, isotope effects, and source of oxygen, etc., between NADPH/O2- and PhIO-supported P450 reactions have been generally attributed to reasons other than the mechanistic differences between the two systems. In the present study, we have used a series of sensitive mechanistic probes, 4-chloro-N-cyclopropyl-N-alkylanilines, to compare and contrast the chemistries of the NADPH/O2- and PhIO-supported purified CYP2B1 N-dealkylation reactions. Herein we present the first experimental evidence to demonstrate that the NADPH/O2- and PhIO-supported P450 N-dealkylations are mechanistically distinct and, thus, the P450/PhIO system may not be a good mechanistic model for P450/NADPH/O2-catalyzed N-dealkylations. en_US
dc.description.sponsorship NCI NIH HHS/ NIGMS NIH HHS en_US
dc.format.extent 1376-7 en_US
dc.language.iso eng en_US
dc.publisher American Chemical Society en_US
dc.relation.ispartofseries Journal of the American Chemical Society en_US
dc.relation.ispartofseries J. Am. Chem. Soc. en_US
dc.source NLM en_US
dc.subject Research Support, U.S. Gov't, P.H.S. en_US
dc.subject.mesh Alkylation en_US
dc.subject.mesh Catalysis en_US
dc.subject.mesh Cytochrome P-450 CYP2B1/chemistry en_US
dc.subject.mesh Iodobenzenes/chemistry en_US
dc.subject.mesh NADP/chemistry en_US
dc.subject.mesh Oxidation-Reduction en_US
dc.subject.mesh Oxygen/chemistry en_US
dc.subject.mesh Cytochrome P-450 CYP2B1/metabolism en_US
dc.subject.mesh Iodobenzenes/metabolism en_US
dc.subject.mesh NADP/metabolism en_US
dc.subject.mesh Oxygen/metabolism en_US
dc.title P(450)/NADPH/O(2)- and P(450)/PhIO-catalyzed N-dealkylations are mechanistically distinct en_US
dc.type Article en_US
dc.coverage.spacial United States en_US
dc.description.version peer reviewed en_US
dc.rights.holder Copyright © 2005 American Chemical Society en_US

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