Evidence for CCl/CBr⋅⋅⋅π Interactions as an Important Contribution to Protein–Ligand Binding Affinity (pages 2911–2916)
Hans Matter, Marc Nazaré, Stefan Güssregen, David W. Will, Herman Schreuder, Armin Bauer, Matthias Urmann, Kurt Ritter, Michael Wagner and Volkmar Wehner
Article first published online: 17 MAR 2009 | DOI: 10.1002/anie.200806219
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).