Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: The same but for different reasons

被引：26

作者：

Gerlach, Christof

Smolinski, Michael

Steuber, Holger

Sotriffer, Christoph A.

Heine, Andreas

Hangauer, David G.

Klebe, Gerhard

机构：

[1] Univ Marburg, Inst Pharmaceut Chem, D-35032 Marburg, Germany

[2] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA

[3] Univ Wurzburg, Inst Pharm & Lebensmittelchem, D-97074 Wurzburg, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2007年 / 46卷 / 44期

关键词：

drug design; isothermal titration calorimetry; lead structure optimization; thermodynamics; thrombin;

D O I：

10.1002/anie.200701169

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Graph Presented) Small changes, big effects: Two thrombin inhibitors (see picture; R = cyclopentyl (1a), R = cyclohexyl (1b)) 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). © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

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页码：8511 / 8514

页数：4

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