Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils

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dc.contributor Wichita State University. Department of Chemistry en_US
dc.contributor.author Groutas, William C. en_US
dc.contributor.author Huang, He en_US
dc.contributor.author Epp, Jeffrey B. en_US
dc.contributor.author Venkataraman, Radhika en_US
dc.contributor.author McClenahan, Jerry J. en_US
dc.contributor.author Tagusagawa, F. en_US
dc.date.accessioned 2012-02-06T17:15:25Z
dc.date.available 2012-02-06T17:15:25Z
dc.date.issued 1994-11-29 en_US
dc.identifier 7986820 en_US
dc.identifier 0217513 en_US
dc.identifier HL 38048 en_US
dc.identifier.citation Biochimica et biophysica acta. 1994 Nov 29; 1227(3): 130-6. en_US
dc.identifier.issn 0006-3002 en_US
dc.identifier.uri http://hdl.handle.net/10057/4236
dc.description Full text of this article is not available in SOAR. en_US
dc.description.abstract A series of dihydrouracil derivatives has been synthesized and investigated for their in vitro inhibitory activity toward human leukocyte elastase (HLE) and cathepsin G (Cath G). Alkyl [sulfonyl(oxy)] uracils 1-2 were found to be efficient, time-dependent inhibitors of elastase (kobs/[I] M-1 s-1 values ranged between 480 and 8110). These compounds formed acyl enzymes that exhibited variable hydrolytic stability which appeared to be dependent on the nature of the R1 group (believed to be accommodated at the primary specificity site, S1). The acyl enzymes formed with cathepsin G deacylated rapidly, leading to a significant regain of enzymatic activity. In sharp contrast, the corresponding phosphorus compounds 3-4 were found to be potent, time-dependent irreversible inhibitors of HLE. Furthermore, the results of the structure-activity relationship studies suggest that the binding modes of compounds 1-2 and 3-4 may be different. en_US
dc.description.sponsorship NHLBI NIH HHS en_US
dc.format.extent 130-6 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 Research Support, U.S. Gov't, P.H.S. en_US
dc.subject.lcsh Leukocytes/enzymology en_US
dc.subject.lcsh Uracil/chemical synthesis en_US
dc.subject.lcsh Uracil/chemistry en_US
dc.subject.lcsh Uracil/pharmacology en_US
dc.subject.mesh Cathepsin G en_US
dc.subject.mesh Cathepsins/antagonists & inhibitors en_US
dc.subject.mesh Drug Design en_US
dc.subject.mesh Humans en_US
dc.subject.mesh Leukocyte Elastase/antagonists & inhibitors en_US
dc.subject.mesh Leukocytes/drug effects en_US
dc.subject.mesh Magnetic Resonance Spectroscopy en_US
dc.subject.mesh Models, Molecular en_US
dc.subject.mesh Pancreatic Elastase/antagonists & inhibitors en_US
dc.subject.mesh Serine Endopeptidases en_US
dc.subject.mesh Structure-Activity Relationship en_US
dc.subject.mesh Uracil/analogs & derivatives en_US
dc.title Mechanism-based inhibition of human leukocyte elastase and cathepsin G by substituted dihydrouracils en_US
dc.type Article en_US
dc.coverage.spacial Netherlands en_US
dc.description.version peer reviewed en_US
dc.rights.holder Copyright © 1994, Elsevier en_US

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