Development of peptidyl α-keto-β-aldehydes as new inhibitors of cathepsin L -: Comparisons of potency and selectivity profiles with cathepsin B

被引：21

作者：

Lynas, JF ^{[1
]}

Hawthorne, SJ ^{[1
]}

Walker, B ^{[1
]}

机构：

[1] Queens Univ Belfast, Sch Pharm, Div Biomed Chem, Ctr Med Biol, Belfast BT9 7BL, Antrim, North Ireland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(00)00340-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl alpha-keto-beta-aldehydes. Kinetic evaluation of those compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a K-i=0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1771 / 1773

页数：3

共 20 条

[1] BARRETT AJ, 1981, METHOD ENZYMOL, V80, P535
[2] Human cathepsin O-2, a matrix protein-degrading cysteine protease expressed in osteoclasts - Functional expression of human cathepsin O-2 in Spodoptera frugiperda and characterization of the enzyme
Bromme, D
Okamoto, K
Wang, BB
Biroc, S
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (04) : 2126 - 2132
[3] TIGHT-BINDING INHIBITORS .1. KINETIC-BEHAVIOR
CHA, S
[J]. BIOCHEMICAL PHARMACOLOGY, 1975, 24 (23) : 2177 - 2185
[4] OXIDATION OF ALPHA-DIAZOKETONES DERIVED FROM L-AMINO-ACIDS AND DIPEPTIDES USING DIMETHYLDIOXIRANE - SYNTHESIS AND REACTIONS OF HOMOCHIRAL N-PROTECTED ALPHA-AMINO GLYOXALS
DARKINS, P
MCCARTHY, N
MCKERVEY, MA
YE, T
[J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1993, (15) : 1222 - 1223
[5] THE EFFECTS OF INHIBITORS OF CYSTEINE-PROTEINASES AND COLLAGENASE ON THE RESORPTIVE ACTIVITY OF ISOLATED OSTEOCLASTS
DELAISSE, JM
BOYDE, A
MACONNACHIE, E
ALI, NN
SEAR, CHJ
EECKHOUT, Y
VAES, G
JONES, SJ
[J]. BONE, 1987, 8 (05) : 305 - 313
[6] The crystal structure of human cathepsin L complexed with E-64
Fujishima, A
Imai, Y
Nomura, T
Fujisawa, Y
Yamamoto, Y
Sugawara, T
[J]. FEBS LETTERS, 1997, 407 (01) : 47 - 50
[7] MOLECULAR AND CELLULAR MECHANISMS OF JOINT DESTRUCTION IN RHEUMATOID-ARTHRITIS - 2 CELLULAR MECHANISMS EXPLAIN JOINT DESTRUCTION
GAY, S
GAY, RE
KOOPMAN, WJ
[J]. ANNALS OF THE RHEUMATIC DISEASES, 1993, 52 : S39 - S47
[8] GREEN GDJ, 1981, J BIOL CHEM, V256, P1923
[9] PARTICIPATION OF CATHEPSIN-L ON BONE-RESORPTION
KAKEGAWA, H
NIKAWA, T
TAGAMI, K
KAMIOKA, H
SUMITANI, K
KAWATA, T
DROBNICKOSOROK, M
LENARCIC, B
TURK, V
KATUNUMA, N
[J]. FEBS LETTERS, 1993, 321 (2-3) : 247 - 250
[10] RAPID INACTIVATION OF CATHEPSIN-L BY Z-PHE-PHECHN2-1 AND Z-PHE-ALACHN2
KIRSCHKE, H
SHAW, E
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1981, 101 (02) : 454 - 458

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