FEBS Letters | |
Substrate and inhibitor studies on proteinase 3 | |
Dolman, Koert M.1  Kam, Chih-Min2  Kerrigan, John E.2  Powers, James C.2  Von dem Borne, Albert E.G.Kr.1  Goldschmeding, Roel1  | |
[1] Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Laboratory for Experimental and Clinical Immunology and Department of Hematology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA | |
关键词: Peptide chloromethyl ketone; Peptide phosphonate; Proteinase 3; Substituted isocoumarin; Peptide thioester; Abu; α-aminobutanoic acid; Boc; t-butyloxycarbonyl; 3-BrEtOIC; 3-(2-bromoethoxy)isocoumarin; DCI; 3.4-dichloroisocoumarin; DFP; diisopropyl fluorophosphate; 3-EtOIC; 3-ethoxyisocoumarin; HEPES; 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid; HNE; human neutrophil elastase; MeO; Methoxy; Nva; Norvaline; PIPES; piperazine-N; N-bis(2-ethanesulfonic acid); PMSF; phenylmethanesulfonyl fluoride; 3-PrOIC; 3-propoxyisocoumarin; pNA; p-nitroanilide; PPE; porcine pancreatic elastase; ONp; p-nitrophenylester; SBzl; thiobenzyl ester; | |
DOI : 10.1016/0014-5793(92)80340-M | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Various amino acid and peptide thioesters were tested as substrates for human proteinase 3 and the best substrate is Boc-Ala-Ala-Nva-SBzl with a k cal/K m value of 1.0 × 106nMit-1sit-1 Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with k cal/K m values of (1-4) × 105 M−1 s−1. Substituted isocoumarins are potent inhibitors of proteinase 3 and the best inhibitors are 7-amino-4-chloro-3-(2-bromoethoxy)isocoumarin and 3.4-dichloroisocoumarin (DCI) with k obs/[I] values of 4700 and 2600 M−1 s−1, respectively. Substituted isocoumarins. peptide phosphonates and chloromethyl ketones inhibited proteinase 3 less potently than human neutrophil elastase (HNE) by 1-2 orders of magnitude.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912020295889ZK.pdf | 514KB | download |