| dc.contributor |
Wichita State University. Department of Chemistry |
en_US |
| dc.contributor.author |
Groutas, William C. |
en_US |
| dc.contributor.author |
Venkataraman, Radhika |
en_US |
| dc.contributor.author |
Brubaker, Michael J. |
en_US |
| dc.contributor.author |
Epp, Jeffrey B. |
en_US |
| dc.contributor.author |
Chong, Lee S. |
en_US |
| dc.contributor.author |
Stanga, Michael A. |
en_US |
| dc.contributor.author |
McClenahan, Jerald J. |
en_US |
| dc.contributor.author |
Tagusagawa, F. |
en_US |
| dc.date.accessioned |
2012-02-06T17:15:24Z |
|
| dc.date.available |
2012-02-06T17:15:24Z |
|
| dc.date.issued |
1993-08-07 |
en_US |
| dc.identifier |
8343527 |
en_US |
| dc.identifier |
0217513 |
en_US |
| dc.identifier |
HL 38048 |
en_US |
| dc.identifier.citation |
Biochimica et biophysica acta. 1993 Aug 7; 1164(3): 283-8. |
en_US |
| dc.identifier.issn |
0006-3002 |
en_US |
| dc.identifier.uri |
http://hdl.handle.net/10057/4234 |
|
| dc.description |
Full text of this article is not available in SOAR. |
en_US |
| dc.description.abstract |
A series of 3-(alkylthio)-N-hydroxysuccinimide derivatives was synthesized and their inhibitory activity towards human leukocyte elastase (HLE) was investigated. The interaction of the compounds having a 3-alkylthioether side chain (compounds 1 and 2) with HLE was found to involve rapid acylation of the enzyme, followed by total regain of enzymatic activity within 3 h. Interestingly, compounds 3-8, having an oxidized thioether side chain, were found to be highly effective, time-dependent, irreversible inhibitors of the enzyme. The k(obs)/I values for compounds 3-8 ranged between 890 and 24,000 M-1 s-1. These findings demonstrate that, unlike the physiological inhibitor of HLE (alpha-1-proteinase inhibitor), which is inactivated upon oxidation, low-molecular-weight compounds retain and/or show enhanced inhibitory activity towards HLE upon oxidation of the thioether side chain and lay the groundwork for the development of compounds that embody proteinase inhibitory and antioxidant activity. |
en_US |
| dc.description.sponsorship |
NHLBI NIH HHS |
en_US |
| dc.format.extent |
283-8 |
en_US |
| dc.language.iso |
eng |
en_US |
| dc.publisher |
Elsevier |
en_US |
| dc.relation.ispartofseries |
Biochimica et biophysica acta |
en_US |
| dc.relation.ispartofseries |
Biochim. Biophys. Acta |
en_US |
| dc.source |
NLM |
en_US |
| dc.subject |
Comparative Study |
en_US |
| dc.subject |
Research Support, U.S. Gov't, P.H.S. |
en_US |
| dc.subject.mesh |
Acylation |
en_US |
| dc.subject.mesh |
Enzyme Inhibitors/chemical synthesis |
en_US |
| dc.subject.mesh |
Humans |
en_US |
| dc.subject.mesh |
Leukocytes/enzymology |
en_US |
| dc.subject.mesh |
Models, Molecular |
en_US |
| dc.subject.mesh |
Pancreatic Elastase/antagonists & inhibitors |
en_US |
| dc.subject.mesh |
Structure-Activity Relationship |
en_US |
| dc.subject.mesh |
Succinimides/chemistry |
en_US |
| dc.subject.mesh |
Sulfides/chemical synthesis |
en_US |
| dc.subject.mesh |
alpha 1-Antitrypsin/pharmacology |
en_US |
| dc.subject.mesh |
Succinimides/chemical synthesis |
en_US |
| dc.subject.mesh |
Succinimides/pharmacology |
en_US |
| dc.subject.mesh |
Sulfides/chemistry |
en_US |
| dc.title |
3-(Alkylthio)-N-hydroxysuccinimide derivatives: potent inhibitors of human leukocyte elastase |
en_US |
| dc.type |
Article |
en_US |
| dc.coverage.spacial |
Netherlands |
en_US |
| dc.description.version |
peer reviewed |
en_US |
| dc.rights.holder |
Copyright © 1993, Elsevie |
en_US |