Halogen Bonding in Nucleic Acid Complexes

J Med Chem. 2017 Nov 9;60(21):8681-8690. doi: 10.1021/acs.jmedchem.7b00329. Epub 2017 Jun 23.

Abstract

Halogen bonding (X-bonding) has attracted notable attention among noncovalent interactions. This highly directional attraction between a halogen atom and an electron donor has been exploited in knowledge-based drug design. A great deal of information has been gathered about X-bonds in protein-ligand complexes, as opposed to nucleic acid complexes. Here we provide a thorough analysis of nucleic acid complexes containing either halogenated building blocks or halogenated ligands. We analyzed close contacts between halogens and electron-rich moieties. The phosphate backbone oxygen is clearly the most common halogen acceptor. We identified 21 X-bonds within known structures of nucleic acid complexes. A vast majority of the X-bonds is formed by halogenated nucleobases, such as bromouridine, and feature excellent geometries. Noncovalent ligands have been found to form only interactions with suboptimal interaction geometries. Hence, the first X-bonded nucleic acid binder remains to be discovered.

MeSH terms

  • Bromouracil / analogs & derivatives
  • Halogens / chemistry*
  • Ligands
  • Nucleic Acids / chemistry*
  • Nucleosides / chemistry
  • Oxygen / chemistry
  • Phosphates / chemistry
  • Uridine / analogs & derivatives
  • Uridine / chemistry

Substances

  • Halogens
  • Ligands
  • Nucleic Acids
  • Nucleosides
  • Phosphates
  • Bromouracil
  • 5-bromouridine
  • Oxygen
  • Uridine