Evidence for C-Cl/C-Br•••π Interactions as an Important Contribution to Protein-Ligand Binding Affinity

被引：238

作者：

Matter, Hans ^{[1
]}

Nazare, Marc ^{[1
]}

Guessregen, Stefan ^{[1
]}

Will, David W. ^{[1
]}

Schreuder, Herman ^{[1
]}

Bauer, Armin ^{[1
]}

Urmann, Matthias ^{[1
]}

Ritter, Kurt ^{[1
]}

Wagner, Michael ^{[1
]}

Wehner, Volkmar ^{[1
]}

机构：

[1] Sanofi Aventis Deutschland GmbH, Discovery Res Ind Pk Hochst, D-65926 Frankfurt, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2009年 / 48卷 / 16期

关键词：

ab initio calculations; halogens; inhibitors; noncovalent interactions; pi interactions; X-RAY CRYSTALLOGRAPHY; MEDICINAL CHEMISTRY; BENZENE DIMER; THROMBIN INHIBITORS; CRYSTAL-STRUCTURES; FLUORINE SCAN; ACTIVE-SITE; FORCE-FIELD; DRUG DESIGN; HALOGEN;

D O I：

10.1002/anie.200806219

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Attractive chlorine: Noncovalent interactions between chlorine or bromine atoms and aromatic rings in proteins open up a new method for the manipulation of molecular recognition. Substitution at distinct positions of two factor Xa inhibitors improves the free energy of binding by interaction with a tyrosine unit. The generality of this motif was underscored by multiple crystal structures as well as high-level quantum chemical calculations (see picture). © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：2911 / 2916

页数：6

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