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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorGroutas, William C.en_US
dc.contributor.authorHe, Shuen_US
dc.contributor.authorKuang, Rongzeen_US
dc.contributor.authorRuan, Sumeien_US
dc.contributor.authorTu, Juanen_US
dc.contributor.authorChan, Ho-Kiten_US
dc.date.accessioned2012-02-06T17:16:10Z
dc.date.available2012-02-06T17:16:10Z
dc.date.issued2001-06-01en_US
dc.identifier11408173en_US
dc.identifier9413298en_US
dc.identifierS0968089601000372en_US
dc.identifier.citationBioorganic & medicinal chemistry. 2001 Jun; 9(6): 1543-8.en_US
dc.identifier.issn0968-0896en_US
dc.identifier.urihttp://hdl.handle.net/10057/4315
dc.descriptionFull text of this article is not available in SOAR.en_US
dc.description.abstractA challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificity, that is, show a preference for the same P(1) residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both the S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability.en_US
dc.format.extent1543-8en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.ispartofseriesBioorganic & medicinal chemistryen_US
dc.relation.ispartofseriesBioorg. Med. Chem.en_US
dc.sourceNLMen_US
dc.subject.meshCathepsin Gen_US
dc.subject.meshCathepsins/antagonists & inhibitorsen_US
dc.subject.meshCyclic S-Oxides/chemistryen_US
dc.subject.meshDrug Designen_US
dc.subject.meshLeukocyte Elastase/antagonists & inhibitorsen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMyeloblastinen_US
dc.subject.meshSerine Endopeptidases/drug effectsen_US
dc.subject.meshSerine Proteinase Inhibitors/chemistryen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshSulfonamides/chemistryen_US
dc.subject.meshThiazoles/chemistryen_US
dc.subject.meshSerine Proteinase Inhibitors/pharmacologyen_US
dc.titleInhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffolden_US
dc.typeArticleen_US
dc.coverage.spacialEnglanden_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright 2001 by Elsevier Science Ltd.en_US


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