Evidence for C-Cl/C-Br...pi interactions as an important contribution to protein-ligand binding affinity

Angew Chem Int Ed Engl. 2009;48(16):2911-6. doi: 10.1002/anie.200806219.

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).

MeSH terms

  • Binding Sites
  • Bromides / chemistry*
  • Chlorine / chemistry*
  • Crystallography, X-Ray
  • Electrons
  • Factor Xa / chemistry*
  • Factor Xa Inhibitors
  • Indoles / chemistry*
  • Protein Binding
  • Structure-Activity Relationship
  • Thermodynamics
  • Tyrosine / chemistry

Substances

  • Bromides
  • Factor Xa Inhibitors
  • Indoles
  • Tyrosine
  • Chlorine
  • Factor Xa