title: Evidence for C-Cl/C-Br...pi interactions as an important contribution to protein-ligand binding affinity.
abstract: 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).
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Discovery Research, Industriepark Höchst, Building G878, 65926 Frankfurt am Main, Germany. hans.matter@sanofi-aventis.com
authors.forename: Hans
authors.initials: H
authors.lastname: Matter
authors.forename: Marc
authors.initials: M
authors.lastname: Nazaré
authors.forename: Stefan
authors.initials: S
authors.lastname: Güssregen
authors.forename: David W
authors.initials: DW
authors.lastname: Will
authors.forename: Herman
authors.initials: H
authors.lastname: Schreuder
authors.forename: Armin
authors.initials: A
authors.lastname: Bauer
authors.forename: Matthias
authors.initials: M
authors.lastname: Urmann
authors.forename: Kurt
authors.initials: K
authors.lastname: Ritter
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Volkmar
authors.initials: V
authors.lastname: Wehner
mesh_terms: D001665:Binding Sites; D001965:Bromides / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004583:Electrons; D015951:Factor Xa / Q000737:chemistry*; D065427:Factor Xa Inhibitors; D007211:Indoles / Q000737:chemistry*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014443:Tyrosine / Q000737:chemistry
chemical_list: D001965:Bromides; D065427:Factor Xa Inhibitors; D007211:Indoles; D014443:Tyrosine; D002713:Chlorine; D015951:Factor Xa