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

P. Cuniasse; L. Devel; A. Makaritis; F. Beau; D. Georgiadis; M. Matziari; A. Yiotakis; V. Dive

doi:10.1016/j.biochi.2004.09.025

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

P. Cuniasse, L. Devel, A. Makaritis, F. Beau, D. Georgiadis, M. Matziari, A. Yiotakis, V. Dive^*

^*Corresponding author for this work

Department of Chemistry and Materials Science

Research output: Contribution to journal › Review article › peer-review

110 Citations (Scopus)

Abstract

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 MMP active-site, the development of specific MMP 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.

Original language	English
Pages (from-to)	393-402
Number of pages	10
Journal	Biochimie
Volume	87
Issue number	3-4 SPEC. ISS.
DOIs	https://doi.org/10.1016/j.biochi.2004.09.025
Publication status	Published - 2005

Keywords

Conformational variability
Inhibitor selectivity
Inhibitors
MMPs
Zinc protease

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10.1016/j.biochi.2004.09.025

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title = "Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs",

abstract = "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 MMP active-site, the development of specific MMP 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.",

keywords = "Conformational variability, Inhibitor selectivity, Inhibitors, MMPs, Zinc protease",

author = "P. Cuniasse and L. Devel and A. Makaritis and F. Beau and D. Georgiadis and M. Matziari and A. Yiotakis and V. Dive",

note = "Funding Information: This work was supported by funds from the Commissariat {\`a} l{\textquoteright}Energie Atomique and from the European Commission (FP5RDT, QLK3-CT02-02136 and FP6RDT, LSHC-CT-2003-503297. All figures were produced with the PyMOL Software v0.95 [69] .",

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T1 - Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs

AU - Cuniasse, P.

AU - Devel, L.

AU - Makaritis, A.

AU - Beau, F.

AU - Georgiadis, D.

AU - Matziari, M.

AU - Yiotakis, A.

AU - Dive, V.

N1 - Funding Information: This work was supported by funds from the Commissariat à l’Energie Atomique and from the European Commission (FP5RDT, QLK3-CT02-02136 and FP6RDT, LSHC-CT-2003-503297. All figures were produced with the PyMOL Software v0.95 [69] .

PY - 2005

Y1 - 2005

N2 - 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 MMP active-site, the development of specific MMP 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.

AB - 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 MMP active-site, the development of specific MMP 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.

KW - Conformational variability

KW - Inhibitor selectivity

KW - Inhibitors

KW - MMPs

KW - Zinc protease

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DO - 10.1016/j.biochi.2004.09.025

M3 - Review article

C2 - 15781327

AN - SCOPUS:15244350894

SN - 0300-9084

VL - 87

SP - 393

EP - 402

JO - Biochimie

JF - Biochimie

IS - 3-4 SPEC. ISS.

ER -

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

Abstract

Keywords

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