Systematic Investigation of Halogen Bonding in Protein-Ligand Interactions

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, str...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2011-01, Vol.50 (1), p.314-318
Main Authors: Hardegger, Leo A., Kuhn, Bernd, Spinnler, Beat, Anselm, Lilli, Ecabert, Robert, Stihle, Martine, Gsell, Bernard, Thoma, Ralf, Diez, Joachim, Benz, Jörg, Plancher, Jean-Marc, Hartmann, Guido, Banner, David W., Haap, Wolfgang, Diederich, François
Format: Article
Language:English
Subjects:
Bonding strength
Catalytic Domain
Cathepsin L
Chemistry, Pharmaceutical - methods
Fluorine
halogen bonding
Halogens - analysis
Halogens - chemistry
Halogens - metabolism
Ligands
medicinal chemistry
molecular recognition
protein-ligand interactions
Proteins - analysis
Proteins - chemistry
Proteins - metabolism
Structure-Activity Relationship
structure-activity relationships
Thermodynamics
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Summary: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.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201006781