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rdf:type |
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lifeskim:mentions |
umls-concept:C0014898,
umls-concept:C0022634,
umls-concept:C0027950,
umls-concept:C0030306,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0054868,
umls-concept:C0064833,
umls-concept:C0086418,
umls-concept:C0220781,
umls-concept:C0243077,
umls-concept:C1135183,
umls-concept:C1883254
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pubmed:issue |
1
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pubmed:dateCreated |
1990-2-22
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pubmed:abstractText |
Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CTSG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin G,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Ctsg protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ketones,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Elastase,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
394-407
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:2296031-Amino Acid Sequence,
pubmed-meshheading:2296031-Animals,
pubmed-meshheading:2296031-Cathepsin G,
pubmed-meshheading:2296031-Cathepsins,
pubmed-meshheading:2296031-Chemical Phenomena,
pubmed-meshheading:2296031-Chemistry,
pubmed-meshheading:2296031-Humans,
pubmed-meshheading:2296031-Ketones,
pubmed-meshheading:2296031-Kinetics,
pubmed-meshheading:2296031-Molecular Sequence Data,
pubmed-meshheading:2296031-Molecular Structure,
pubmed-meshheading:2296031-Neutrophils,
pubmed-meshheading:2296031-Oligopeptides,
pubmed-meshheading:2296031-Pancreas,
pubmed-meshheading:2296031-Pancreatic Elastase,
pubmed-meshheading:2296031-Protease Inhibitors,
pubmed-meshheading:2296031-Rats,
pubmed-meshheading:2296031-Serine Endopeptidases,
pubmed-meshheading:2296031-Stereoisomerism,
pubmed-meshheading:2296031-Swine
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pubmed:year |
1990
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pubmed:articleTitle |
Synthesis of peptidyl fluoromethyl ketones and peptidyl alpha-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G.
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pubmed:affiliation |
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
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pubmed:publicationType |
Journal Article,
Comparative Study
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