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 |