Thermodynamic Inhibition Profile of a Cyclopentyl and a Cyclohexyl Derivative towards Thrombin: The Same but for Different Reasons

Thermodynamic Inhibition Profile of a Cyclopentyl and a Cyclohexyl Derivative towards Thrombin: The Same but for Different Reasons

Small changes, big effects: Two thrombin inhibitors (see picture; R=cyclopentyl (1 a), R=cyclohexyl (1 b)) were characterized thermodynamically and computationally to explain their identical binding constants. Surprisingly, the free energy of binding is achieved with different enthalpic and entropic...

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Veröffentlicht in:Angewandte Chemie (International ed.) 2007-01, Vol.46 (44), p.8511-8514
Hauptverfasser: Gerlach, Christof, Smolinski, Michael, Steuber, Holger, Sotriffer, Christoph A, Heine, Andreas, Hangauer, David G, Klebe, Gerhard
Format: Artikel
Sprache:eng
Schlagworte:
Azetidines - chemistry
Benzylamines - chemistry
Calorimetry - methods
Chemistry - methods
Chemistry, Pharmaceutical - methods
Crystallography, X-Ray - methods
Cyclohexanes - chemistry
Cyclopentanes - chemistry
Drug Design
Humans
isothermal titration calorimetry
Kinetics
lead structure optimization
Ligands
Models, Chemical
Molecular Conformation
Thermodynamics
thrombin
Thrombin - antagonists & inhibitors
Thrombin - chemistry
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Zusammenfassung:Small changes, big effects: Two thrombin inhibitors (see picture; R=cyclopentyl (1 a), R=cyclohexyl (1 b)) were characterized thermodynamically and computationally to explain their identical binding constants. Surprisingly, the free energy of binding is achieved with different enthalpic and entropic contributions (see plot).
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.200701169