Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs

被引：96

作者：

Cuniasse, P

Devel, L

Makaritis, A

Beau, F

Georgiadis, D

Matziari, A

Yiotakis, A

Dive, V ^{[1
]}

机构：

[1] CEA Saclay, Dept Ingn Etudes Prot, F-91191 Gif Sur Yvette, France

[2] Univ Athens, Organ Chem Lab, Dept Organ Chem, Athens 15771, Greece

来源：

BIOCHIMIE | 2005年 / 87卷 / 3-4期

关键词：

MMPs; inhibitors; zinc protease; conformational variability; inhibitor selectivity;

D O I：

10.1016/j.biochi.2004.09.025

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：

Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of NIMP active-site, the development of specific NIMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity. (c) 2004 Elsevier SAS. All rights reserved.

引用

页码：393 / 402

页数：10

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