1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases

SOAR Repository

Show simple item record

dc.contributor Wichita State University. Department of Chemistry en_US
dc.contributor.author Groutas, William C. en_US
dc.contributor.author Epp, Jeffrey B. en_US
dc.contributor.author Kuang, Rongze en_US
dc.contributor.author Ruan, Sumei en_US
dc.contributor.author Chong, Lee S. en_US
dc.contributor.author Venkataraman, Radhika en_US
dc.contributor.author Tu, Juan en_US
dc.contributor.author He, Shu en_US
dc.contributor.author Yu, Hongyi en_US
dc.contributor.author Fu, Qingfong en_US
dc.contributor.author Li, Yue He en_US
dc.contributor.author Truong, Tien M. en_US
dc.contributor.author Vu, Nga T. en_US
dc.date.accessioned 2012-02-06T17:15:22Z
dc.date.available 2012-02-06T17:15:22Z
dc.date.issued 2001-01-01 en_US
dc.identifier 11361013 en_US
dc.identifier 0372430 en_US
dc.identifier S0003-9861(00)92139-8 en_US
dc.identifier HL57788 en_US
dc.identifier.citation Archives of biochemistry and biophysics. 2001 Jan 1; 385(1): 162-9. en_US
dc.identifier.issn 0003-9861 en_US
dc.identifier.uri http://dx.doi.org/10.1006/abbi.2000.2139 en_US
dc.identifier.uri http://hdl.handle.net/10057/4231
dc.description Click on the DOI link below to access the article (may not be free). en_US
dc.description.abstract The 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold (I) embodies a motif that allows it to dock to the active site of (chymo)trypsin-like proteases in a predictable and substrate-like fashion. Consequently, inhibitors derived from this heterocyclic scaffold interact with both the S and S' subsites of an enzyme. Exploitation of binding interactions with both the S and S' subsites of a target enzyme may lead to compounds with greatly enhanced enzyme selectivity and inhibitory potency. This preliminary report describes the use of a series of compounds having the heterocyclic scaffold linked to various amino acids to probe the S' subsites of human leukocyte elastase (HLE), proteinase 3 (PR 3), and cathepsin G (Cat G). For comparative purposes, a series of compounds derived from a related scaffold, isothiazolidin-3-one 1,1 dioxide (II), was also generated. Several of the compounds were found to be highly potent and selective time-dependent inhibitors of HLE, PR 3, and Cat G. en_US
dc.description.sponsorship NHLBI NIH HHS en_US
dc.format.extent 162-9 en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Archives of biochemistry and biophysics en_US
dc.relation.ispartofseries Arch. Biochem. Biophys. en_US
dc.source NLM en_US
dc.subject Research Support, Non-U.S. Gov't en_US
dc.subject Research Support, U.S. Gov't, P.H.S. en_US
dc.subject.mesh Cathepsin G en_US
dc.subject.mesh Cathepsins/chemistry en_US
dc.subject.mesh Chymotrypsin/chemistry en_US
dc.subject.mesh Cyclic S-Oxides/chemistry en_US
dc.subject.mesh Humans en_US
dc.subject.mesh Kinetics en_US
dc.subject.mesh Leukocyte Elastase/chemistry en_US
dc.subject.mesh Models, Chemical en_US
dc.subject.mesh Molecular Probes/chemistry en_US
dc.subject.mesh Myeloblastin en_US
dc.subject.mesh Protein Binding en_US
dc.subject.mesh Serine Endopeptidases/chemistry en_US
dc.subject.mesh Temperature en_US
dc.subject.mesh Thiazoles/chemistry en_US
dc.subject.mesh Time Factors en_US
dc.subject.mesh Cathepsins/metabolism en_US
dc.subject.mesh Leukocyte Elastase/metabolism en_US
dc.subject.mesh Serine Endopeptidases/metabolism en_US
dc.title 1,2,5-Thiadiazolidin-3-one 1,1 dioxide: a powerful scaffold for probing the S' subsites of (chymo)trypsin-like serine proteases 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 © 2001, Elsevier en_US

Files in this item

Files Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record

Search SOAR

Advanced Search


My Account