Design of sensitive fluorogenic substrates for human cathepsin D

被引：46

作者：

Gulnik, SV ^{[1
]}

Suvorov, LI ^{[1
]}

Majer, P ^{[1
]}

Collins, J ^{[1
]}

Kane, BP ^{[1
]}

Johnson, DG ^{[1
]}

Erickson, JW ^{[1
]}

机构：

[1] NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, AIDS VACCINE PROGRAM, FREDERICK, MD 21702 USA

来源：

FEBS LETTERS | 1997年 / 413卷 / 02期

关键词：

cathepsin D; fluorogenic substrate; structure-based modeling;

D O I：

10.1016/S0014-5793(97)00886-7

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：

Cathepsin D is a lysosomal aspartic proteinase that has been implicated in several pathological processes such as breast cancer and Alzheimer's disease, We designed and synthesized a number of quenched fluorogenic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E-NH2, where X=cysteine, methylcysteine, ethylcysteine, tert-butylcysteine, carboxymethylcysteine, methionine, valine or isoleucine, Most of the fluorogenic substrates exhibited greater k(cat)/K-m ratios than the best cathepsin D substrates described so far, Differences in kinetic constants, which were rationalized using structure-based modeling, might make certain substrates useful for particular applications, such as active site titrations or initial velocity determination using a fluorescent plate reader, (C) 1997 Federation of European Biochemical Societies.

引用

页码：379 / 384

页数：6

共 25 条

[1] CRYSTAL-STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN-D - IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN
BALDWIN, ET
BHAT, TN
GULNIK, S
HOSUR, MV
SOWDER, RC
CACHAU, RE
COLLINS, J
SILVA, AM
ERICKSON, JW
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (14) : 6796 - 6800
[2] Barrett A, 1977, PROTEINASES MAMMALIA, P209
[3] BRIOZZO P, 1988, CANCER RES, V48, P3688
[4] CASTALDO AM, 1990, P NATL ACAD SCI USA, V87, P3861
[5] PROCESSING OF THE PRE-BETA-AMYLOID PROTEIN BY CATHEPSIN-D IS ENHANCED BY A FAMILIAL ALZHEIMERS-DISEASE MUTATION
DREYER, RN
BAUSCH, KM
FRACASSO, P
HAMMOND, LJ
WUNDERLICH, D
WIRAK, DO
DAVIS, G
BRINI, CM
BUCKHOLZ, TM
KONIG, G
KAMARCK, ME
TAMBURINI, PP
[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1994, 224 (02): : 265 - 271
[6] A SYSTEMATIC SERIES OF SYNTHETIC CHROMOPHORIC SUBSTRATES FOR ASPARTIC PROTEINASES
DUNN, BM
JIMENEZ, M
PARTEN, BF
VALLER, MJ
ROLPH, CE
KAY, J
[J]. BIOCHEMICAL JOURNAL, 1986, 237 (03) : 899 - 906
[7] CLONING AND SEQUENCE-ANALYSIS OF CDNA FOR HUMAN CATHEPSIN-D
FAUST, PL
KORNFELD, S
CHIRGWIN, JM
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (15) : 4910 - 4914
[8] Fluorogenic peptide substrates for assay of aspartyl proteinases
Filippova, IY
Lysogorskaya, EN
Anisimova, VV
Suvorov, LI
Oksenoit, ES
Stepanov, VM
[J]. ANALYTICAL BIOCHEMISTRY, 1996, 234 (02) : 113 - 118
[9] ISOLATION AND SEQUENCING OF A CDNA CLONE ENCODING RAT-LIVER LYSOSOMAL CATHEPSIN-D AND THE STRUCTURE OF 3 FORMS OF MATURE ENZYMES
FUJITA, H
TANAKA, Y
NOGUCHI, Y
KONO, A
HIMENO, M
KATO, K
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 179 (01) : 190 - 196
[10] Biological and clinical significance of cathepsin D in breast cancer metastasis
Garcia, M
Platet, N
Liaudet, E
Laurent, V
Derocq, D
Brouillet, JP
Rochefort, H
[J]. STEM CELLS, 1996, 14 (06) : 642 - 650

← 1 2 3 →