Evidence for C-Cl/C-Br...pi interactions as an important contribution to protein-ligand binding affinity.
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).
Matter
Hans
H
Sanofi-Aventis Deutschland GmbH, Discovery Research, Industriepark Höchst, Building G878, 65926 Frankfurt am Main, Germany. hans.matter@sanofi-aventis.com
Nazaré
Marc
M
Güssregen
Stefan
S
Will
David W
DW
Schreuder
Herman
H
Bauer
Armin
A
Urmann
Matthias
M
Ritter
Kurt
K
Wagner
Michael
M
Wehner
Volkmar
V
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
D001965:Bromides; D065427:Factor Xa Inhibitors; D007211:Indoles; D014443:Tyrosine; D002713:Chlorine; D015951:Factor Xa