Systematic Investigation of Halogen Bonding in Protein–Ligand Interactions (pages 314–318)
Leo A. Hardegger, Dr. Bernd Kuhn, Beat Spinnler, Lilli Anselm, Robert Ecabert, Martine Stihle, Bernard Gsell, Dr. Ralf Thoma, Dr. Joachim Diez, Dr. Jörg Benz, Dr. Jean-Marc Plancher, Dr. Guido Hartmann, Dr. David W. Banner, Dr. Wolfgang Haap and Prof. Dr. François Diederich
Version of Record online: 23 DEC 2010 | DOI: 10.1002/anie.201006781
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 CO 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.