SUBSTRATE AND INHIBITOR STUDIES ON PROTEINASE-3

被引：60

作者：

KAM, CM

KERRIGAN, JE

DOLMAN, KM

GOLDSCHMEDING, R

VONDEMBORNE, AEGK

POWERS, JC

机构：

[1] GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332

[2] NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,AMSTERDAM,NETHERLANDS

[3] UNIV AMSTERDAM,ACAD MED CTR,DEPT HEMATOL,1105 AZ AMSTERDAM,NETHERLANDS

来源：

FEBS LETTERS | 1992年 / 297卷 / 1-2期

关键词：

PEPTIDE CHLOROMETHYL KETONE; PEPTIDE PHOSPHONATE; PROTEINASE-3; SUBSTITUTED ISOCOUMARIN; PEPTIDE THIOESTER;

D O I：

10.1016/0014-5793(92)80340-M

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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(cat)/K(m) value of 1.0 x 10(6) M-1.s-1. Boc-Ala-Ala-AA-SBzl (AA = Val, Ala, or Met) are also good substrates with k(cat)/K(m) values of (1-4) x 10(5) 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.

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页码：119 / 123

页数：5

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