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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2011-5-6
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pubmed:abstractText |
The purpose of this work was to study the reaction kinetics between two model sulfenamide prodrugs of linezolid, N-(phenylthio)linezolid and N-[(2-ethoxycarbonyl)ethylthio]linezolid, with free thiol-containing proteins; commercial human serum albumin (HSA); a constitutively active mutant of the protein tyrosine phosphatase PRL-1 (PRL-1-C170S-C171S), a model protein; and diluted fresh human plasma. The reaction was followed by high-performance liquid chromatography, both for the loss of prodrug and appearance of linezolid, and at different pH values with molar excess of the proteins relative to the prodrugs. Pseudo first-order kinetics was observed. Consistent with earlier findings for the reaction between similar sulfenamides and small-molecule thiols, the reaction kinetics appeared to be consistent with thiolate attack at the sulfenamide bond to release the parent drug. The proteins reacted significantly slower on a molar basis than their small-molecule counterparts. It appears that proteins such as HSA may play a role in the in vivo conversion of sulfenamide prodrugs to their parent drug.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetamides,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazolidinones,
http://linkedlifedata.com/resource/pubmed/chemical/PTP4A1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfamerazine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/linezolid,
http://linkedlifedata.com/resource/pubmed/chemical/sulfenamide
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1520-6017
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association
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pubmed:issnType |
Electronic
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pubmed:volume |
100
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3023-7
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pubmed:meshHeading |
pubmed-meshheading:21547913-Acetamides,
pubmed-meshheading:21547913-Cell Cycle Proteins,
pubmed-meshheading:21547913-Chemistry, Pharmaceutical,
pubmed-meshheading:21547913-Chromatography, High Pressure Liquid,
pubmed-meshheading:21547913-Drug Stability,
pubmed-meshheading:21547913-Humans,
pubmed-meshheading:21547913-Hydrogen-Ion Concentration,
pubmed-meshheading:21547913-Kinetics,
pubmed-meshheading:21547913-Membrane Proteins,
pubmed-meshheading:21547913-Mutation,
pubmed-meshheading:21547913-Oxazolidinones,
pubmed-meshheading:21547913-Plasma,
pubmed-meshheading:21547913-Prodrugs,
pubmed-meshheading:21547913-Protein Tyrosine Phosphatases,
pubmed-meshheading:21547913-Serum Albumin,
pubmed-meshheading:21547913-Sulfamerazine,
pubmed-meshheading:21547913-Sulfhydryl Compounds,
pubmed-meshheading:21547913-Technology, Pharmaceutical
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pubmed:year |
2011
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pubmed:articleTitle |
Reversion of sulfenamide prodrugs in the presence of free thiol-containing proteins.
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pubmed:affiliation |
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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