Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs.
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.
Cuniasse
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P
CEA, Département d'Ingénierie et d'Etudes des Protéines (DIEP), CE-Saclay, 91191 Gif/Yvette cedex, France.
Devel
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L
Makaritis
A
A
Beau
F
F
Georgiadis
D
D
Matziari
M
M
Yiotakis
A
A
Dive
V
V
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D005544:Forecasting; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D015032:Zinc / Q000737:chemistry
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases; D015032:Zinc