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
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.
引用
收藏
页码:119 / 123
页数:5
相关论文
共 27 条
[1]   HUMAN-LEUKOCYTE AND PORCINE PANCREATIC ELASTASE - X-RAY CRYSTAL-STRUCTURES, MECHANISM, SUBSTRATE-SPECIFICITY, AND MECHANISM-BASED INHIBITORS [J].
BODE, W ;
MEYER, E ;
POWERS, JC .
BIOCHEMISTRY, 1989, 28 (05) :1951-1963
[2]   DOWN-REGULATION OF A SERINE PROTEASE, MYELOBLASTIN, CAUSES GROWTH ARREST AND DIFFERENTIATION OF PROMYELOCYTIC LEUKEMIA-CELLS [J].
BORIES, D ;
RAYNAL, MC ;
SOLOMON, DH ;
DARZYNKIEWICZ, Z ;
CAYRE, YE .
CELL, 1989, 59 (06) :959-968
[3]   SUBCELLULAR-LOCALIZATION OF THE B-CYTOCHROME COMPONENT OF THE HUMAN NEUTROPHIL MICROBICIDAL OXIDASE - TRANSLOCATION DURING ACTIVATION [J].
BORREGAARD, N ;
HEIPLE, JM ;
SIMONS, ER ;
CLARK, RA .
JOURNAL OF CELL BIOLOGY, 1983, 97 (01) :52-61
[4]   CLONING OF CDNA FOR PROTEINASE-3 - A SERINE PROTEASE, ANTIBIOTIC, AND AUTOANTIGEN FROM HUMAN NEUTROPHILS [J].
CAMPANELLI, D ;
MELCHIOR, M ;
FU, YP ;
NAKATA, M ;
SHUMAN, H ;
NATHAN, C ;
GABAY, JE .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (06) :1709-1715
[5]   AZUROCIDIN AND A HOMOLOGOUS SERINE PROTEASE FROM NEUTROPHILS - DIFFERENTIAL ANTIMICROBIAL AND PROTEOLYTIC PROPERTIES [J].
CAMPANELLI, D ;
DETMERS, PA ;
NATHAN, CF ;
GABAY, JE .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (03) :904-915
[6]   ANTIBIOTIC PROTEINS OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES [J].
GABAY, JE ;
SCOTT, RW ;
CAMPANELLI, D ;
GRIFFITH, J ;
WILDE, C ;
MARRA, MN ;
SEEGER, M ;
NATHAN, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (14) :5610-5614
[7]   WEGENER GRANULOMATOSIS AUTOANTIBODIES IDENTIFY A NOVEL DIISOPROPYLFLUOROPHOSPHATE BINDING-PROTEIN IN THE LYSOSOMES OF NORMAL HUMAN-NEUTROPHILS [J].
GOLDSCHMEDING, R ;
VANDERSCHOOT, CE ;
HUININK, DT ;
HACK, CE ;
VANDENENDE, ME ;
KALLENBERG, CGM ;
VONDEMBORNE, AEGK .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (05) :1577-1587
[8]   DETERMINATION OF SULFHYDRYL GROUPS WITH 2,2'- OR 4,4'-DITHIODIPYRIDINE [J].
GRASSETTI, DR ;
MURRAY, JF .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1967, 119 (1-3) :41-+
[9]  
GROUTAS WC, 1990, J MED CHEM, V33, P1087
[10]   REACTION OF SERINE PROTEASES WITH SUBSTITUTED ISOCOUMARINS - DISCOVERY OF 3,4-DICHLOROISOCOUMARIN, A NEW GENERAL MECHANISM BASED SERINE PROTEASE INHIBITOR [J].
HARPER, JW ;
HEMMI, K ;
POWERS, JC .
BIOCHEMISTRY, 1985, 24 (08) :1831-1841