| dc.contributor |
Wichita State University. Department of Chemistry |
en_US |
| dc.contributor.author |
Wong, Tzutshin |
en_US |
| dc.contributor.author |
Groutas, Christopher S. |
en_US |
| dc.contributor.author |
Mohan, Swathi |
en_US |
| dc.contributor.author |
Lai, Zhong |
en_US |
| dc.contributor.author |
Alliston, Kevin R. |
en_US |
| dc.contributor.author |
Vu, Nga T. |
en_US |
| dc.contributor.author |
Schechter, Norman M. |
en_US |
| dc.contributor.author |
Groutas, William C. |
en_US |
| dc.date.accessioned |
2012-02-06T17:15:46Z |
|
| dc.date.available |
2012-02-06T17:15:46Z |
|
| dc.date.issued |
2005-04-01 |
en_US |
| dc.identifier |
15752703 |
en_US |
| dc.identifier |
0372430 |
en_US |
| dc.identifier |
S0003-9861(05)00052-4 |
en_US |
| dc.identifier |
AI 45075/ HL 57788 |
en_US |
| dc.identifier.citation |
Archives of biochemistry and biophysics. 2005 Apr 1; 436(1): 1-7. |
en_US |
| dc.identifier.issn |
0003-9861 |
en_US |
| dc.identifier.uri |
http://dx.doi.org/10.1016/j.abb.2005.01.022 |
en_US |
| dc.identifier.uri |
http://hdl.handle.net/10057/4260 |
|
| dc.description |
Click on the DOI link below to access the article (may not be free). |
en_US |
| dc.description.abstract |
We describe herein the design, synthesis, and in vitro biochemical evaluation of a series of potent, time-dependent inhibitors of the mast cell-derived serine protease tryptase. The inhibitors were readily obtained by attaching various heterocyclic thiols, as well as a basic primary specificity residue P(1), to the 1,2,5-thiadiazolidin-3-one 1,1-dioxide scaffold. The inhibitors were found to be devoid of any inhibitory activity toward a neutral (elastase) or cysteine (papain) protease, however they were also fairly efficient inhibitors of bovine trypsin. The differential inhibition observed with trypsin suggests that enzyme selectivity can be optimized by exploiting differences in the S' subsites of the two enzymes. The results described herein demonstrate the versatility of the heterocyclic scaffold in fashioning mechanism-based inhibitors of neutral, basic, and acidic (chymo)trypsin-like serine proteases. |
en_US |
| dc.description.sponsorship |
NIAID NIH HHS/ NHLBI NIH HHS |
en_US |
| dc.format.extent |
1-7 |
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 |
Animals |
en_US |
| dc.subject.mesh |
Cattle |
en_US |
| dc.subject.mesh |
Chymotrypsin/chemistry |
en_US |
| dc.subject.mesh |
Cyclic S-Oxides/pharmacology |
en_US |
| dc.subject.mesh |
Dose-Response Relationship, Drug |
en_US |
| dc.subject.mesh |
Heterocyclic Compounds/pharmacology |
en_US |
| dc.subject.mesh |
Humans |
en_US |
| dc.subject.mesh |
Leukocyte Elastase/antagonists & inhibitors |
en_US |
| dc.subject.mesh |
Papain/antagonists & inhibitors |
en_US |
| dc.subject.mesh |
Serine Endopeptidases/drug effects |
en_US |
| dc.subject.mesh |
Serine Proteinase Inhibitors/chemical synthesis |
en_US |
| dc.subject.mesh |
Sulfides/pharmacology |
en_US |
| dc.subject.mesh |
Thiadiazoles/chemical synthesis |
en_US |
| dc.subject.mesh |
Time Factors |
en_US |
| dc.subject.mesh |
Tryptases |
en_US |
| dc.subject.mesh |
Leukocyte Elastase/drug effects |
en_US |
| dc.subject.mesh |
Serine Endopeptidases/metabolism |
en_US |
| dc.subject.mesh |
Serine Proteinase Inhibitors/pharmacology |
en_US |
| dc.subject.mesh |
Thiadiazoles/pharmacology |
en_US |
| dc.title |
1,2,5-Thiadiazolidin-3-one 1,1-dioxide-based heterocyclic sulfides are potent inhibitors of human tryptase |
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 © 2005, Elsevier |
en_US |