| 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 |