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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorGroutas, William C.en_US
dc.contributor.authorHuang, Heen_US
dc.contributor.authorEpp, Jeffrey B.en_US
dc.contributor.authorVenkataraman, Radhikaen_US
dc.contributor.authorMcClenahan, Jerry J.en_US
dc.contributor.authorTagusagawa, F.en_US
dc.date.accessioned2012-02-06T17:15:25Z
dc.date.available2012-02-06T17:15:25Z
dc.date.issued1994-11-29en_US
dc.identifier7986820en_US
dc.identifier0217513en_US
dc.identifierHL 38048en_US
dc.identifier.citationBiochimica et biophysica acta. 1994 Nov 29; 1227(3): 130-6.en_US
dc.identifier.issn0006-3002en_US
dc.identifier.urihttp://hdl.handle.net/10057/4236
dc.descriptionFull text of this article is not available in SOAR.en_US
dc.description.abstractA series of dihydrouracil derivatives has been synthesized and investigated for their in vitro inhibitory activity toward human leukocyte elastase (HLE) and cathepsin G (Cath G). Alkyl [sulfonyl(oxy)] uracils 1-2 were found to be efficient, time-dependent inhibitors of elastase (kobs/[I] M-1 s-1 values ranged between 480 and 8110). These compounds formed acyl enzymes that exhibited variable hydrolytic stability which appeared to be dependent on the nature of the R1 group (believed to be accommodated at the primary specificity site, S1). The acyl enzymes formed with cathepsin G deacylated rapidly, leading to a significant regain of enzymatic activity. In sharp contrast, the corresponding phosphorus compounds 3-4 were found to be potent, time-dependent irreversible inhibitors of HLE. Furthermore, the results of the structure-activity relationship studies suggest that the binding modes of compounds 1-2 and 3-4 may be different.en_US
dc.description.sponsorshipNHLBI NIH HHSen_US
dc.format.extent130-6en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesBiochimica et biophysica actaen_US
dc.relation.ispartofseriesBiochim. Biophys. Actaen_US
dc.sourceNLMen_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.lcshLeukocytes/enzymologyen_US
dc.subject.lcshUracil/chemical synthesisen_US
dc.subject.lcshUracil/chemistryen_US
dc.subject.lcshUracil/pharmacologyen_US
dc.subject.meshCathepsin Gen_US
dc.subject.meshCathepsins/antagonists & inhibitorsen_US
dc.subject.meshDrug Designen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukocyte Elastase/antagonists & inhibitorsen_US
dc.subject.meshLeukocytes/drug effectsen_US
dc.subject.meshMagnetic Resonance Spectroscopyen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshPancreatic Elastase/antagonists & inhibitorsen_US
dc.subject.meshSerine Endopeptidasesen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshUracil/analogs & derivativesen_US
dc.titleMechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracilsen_US
dc.typeArticleen_US
dc.coverage.spacialNetherlandsen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 1994, Elsevieren_US


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