NOVEL EPOXYSUCCINYL PEPTIDES - A SELECTIVE INHIBITOR OF CATHEPSIN-B, INVIVO

被引:198
作者
TOWATARI, T
NIKAWA, T
MURATA, M
YOKOO, C
TAMAI, M
HANADA, K
KATUNUMA, N
机构
[1] UNIV TOKUSHIMA,INST ENZYME RES,DIV ENZYME CHEM,TOKUSHIMA 770,JAPAN
[2] TAISHO PHARMACEUT CO LTD,RES CTR,OMIYA,SAITAMA 330,JAPAN
关键词
CYSTEINE PROTEINASE INHIBITORY E-64 DERIVATIVE; CATHEPSIN-B; CATHEPSIN-L; CATHEPSIN-H; CYSTEINE PROTEINASE;
D O I
10.1016/0014-5793(91)80319-X
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
New derivatives of E-64 (compound CA-030 and CA-074) were tested in vitro and in vivo for selective inhibition of cathepsin B. They exhibited 10 000-30 000 times greater inhibitory effects on purified rat cathepsin B than on cathepsin H and L: their initial K(i) values for cathepsin B were about 2-5 nM, like that of E-64-c, whereas their initial K(i) values for cathepsins H and L were about 40-200-mu-M. In in vivo conditions, such as intraperitoneal injection of compound CA-030 or CA-074 into rats, compound CA-074 is an especially potent selective inhibitor of cathepsin B, whereas compound CA-030 does not show selectivity for cathepsin B, although both compounds CA-030 and CA-074 show complete selectivity for cathepsin B in vitro.
引用
收藏
页码:311 / 315
页数:5
相关论文
共 24 条
[11]  
II K, 1986, AM J PATHOL, V122, P193
[12]   INACTIVATION OF HUMAN ALPHA1 PROTEINASE-INHIBITOR BY THIOL PROTEINASES [J].
JOHNSON, D ;
TRAVIS, J .
BIOCHEMICAL JOURNAL, 1977, 163 (03) :639-+
[13]   ABNORMAL EXPRESSION OF LYSOSOMAL CYSTEINE PROTEINASES IN MUSCLE WASTING DISEASES [J].
KATUNUMA, N ;
KOMINAMI, E .
REVIEWS OF PHYSIOLOGY BIOCHEMISTRY AND PHARMACOLOGY, 1987, 108 :1-20
[14]  
KATUNUMA N, 1989, RBC-CELL BIOL REV, V20, P35
[15]  
KIRSCHKE H, 1977, ACTA BIOL MED GER, V36, P185
[16]  
KIRSCHKE H, 1987, LYSOSOMES THEIR ROLE, P193
[17]  
KOMINAMI E, 1987, AM J PATHOL, V127, P461
[18]   CHARACTERIZATION OF A THIOL PROTEINASE SECRETED BY MALIGNANT HUMAN-BREAST TUMORS [J].
MORT, JS ;
RECKLIES, AD ;
POOLE, AR .
BIOCHIMICA ET BIOPHYSICA ACTA, 1980, 614 (01) :134-143
[19]  
MURATA M, 1991, IN PRESS FEBS LETT
[20]  
NIKAWA T, 1990, SEIKAQ, V62, P953