Systematic Investigation of Halogen Bonding in Protein-Ligand Interactions

被引：281

作者：

Hardegger, Leo A. ^{[3
]}

Kuhn, Bernd ^{[1
]}

Spinnler, Beat ^{[1
]}

Anselm, Lilli ^{[1
]}

Ecabert, Robert ^{[1
]}

Stihle, Martine ^{[1
]}

Gsell, Bernard ^{[1
]}

Thoma, Ralf ^{[1
]}

Diez, Joachim ^{[2
]}

Benz, Joerg ^{[1
]}

Plancher, Jean-Marc ^{[1
]}

Hartmann, Guido ^{[1
]}

Banner, David W. ^{[1
]}

Haap, Wolfgang ^{[1
]}

Diederich, Francois ^{[3
]}

机构：

[1] F Hoffmann La Roche & Cie AG, CH-4070 Basel, Switzerland

[2] Expose GmbH, CH-5313 Klingnau, Switzerland

[3] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2011年 / 50卷 / 01期

关键词：

halogen bonding; medicinal chemistry; molecular recognition; protein-ligand interactions; structure-activity relationships; SUPRAMOLECULAR CHEMISTRY; SIGMA-HOLE; HYDROGEN; INHIBITION; COMPLEXES; GEOMETRY;

D O I：

10.1002/anie.201006781

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Halogen bonding triggers activity: Increasing binding affinity was observed for a series of covalent human Cathepsin L inhibitors by exchanging an aryl ring H atom with Cl, Br, and I, which undergo halogen bonding with the C=O group of Gly61 in the S3 pocket of the enzyme. Fluorine, in contrast, strongly avoids halogen bonding (see scheme). The strong distance and angle dependence of halogen bonding was confirmed for biological systems. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：314 / 318

页数：5

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