From Model Complexes to Metalloprotein Inhibition: A Synergistic Approach to Structure-Based Drug Discovery

From Model Complexes to Metalloprotein Inhibition: A Synergistic Approach to Structure-Based Drug Discovery

A happy marriage: The combination of synthetic model chemistry with computational conformational analysis has revealed the binding of an inhibitor to a medically important metalloenzyme. [(TpPh,Me)Zn(mbt)] (TpPh,Me=hydrotris(3,5‐phenylmethylpyrazolyl)borate, mbt=2‐methoxybenzenethiol) was used to te...

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Veröffentlicht in:Angewandte Chemie International Edition 2003-08, Vol.42 (32), p.3772-3774
Hauptverfasser: Puerta, David T., Schames, Julie R., Henchman, Richard H., McCammon, J. Andrew, Cohen, Seth M.
Format: Artikel
Sprache:eng
Schlagworte:
Binding Sites
bioinorganic chemistry
computer chemistry
Crystallography, X-Ray
Drug Design
Indicators and Reagents
Matrix Metalloproteinase 3 - chemistry
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases - chemistry
metalloproteins
Metals - chemistry
Models, Molecular
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Protein Conformation
Structure-Activity Relationship
zinc
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Zusammenfassung:A happy marriage: The combination of synthetic model chemistry with computational conformational analysis has revealed the binding of an inhibitor to a medically important metalloenzyme. [(TpPh,Me)Zn(mbt)] (TpPh,Me=hydrotris(3,5‐phenylmethylpyrazolyl)borate, mbt=2‐methoxybenzenethiol) was used to template the conformation of a known inhibitor in the active site of the metalloenzyme, as shown by the green ligand inside the active site of the protein (the ZnII ion is shown in purple).
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200351433