DNA-binding drugs caught in action: the latest 3D pictures of drug-DNA complexes

Dalton Trans. 2009 Jan 21;(3):399-414. doi: 10.1039/b809873p. Epub 2008 Nov 7.


In this paper, we review recent DNA-binding agents that are expected to influence the field of DNA-targeting. We restrict ourselves to binders for which the three-dimensional structure in complex with DNA or RNA has been determined by X-ray crystallography or NMR. Furthermore, we primarily focus on unprecedented ways of targeting peculiar DNA structures, such as junctions, quadruplexes, and duplex DNAs different from the B-form. Classical binding modes of small molecular weight compounds to DNA, i.e. groove binding, intercalation and covalent addition are discussed in those cases where the structures represent a novelty. In addition, we review 3D structures of triple-stranded DNA, of the so-called Peptide Nucleic Acids (PNAs), which are oligonucleotide bases linked by a polypeptide backbone, and of aptamers, which are DNA or RNA receptors that are designed combinatorially. A discussion on perspectives in the field of DNA-targeting and on sequence recognition is also provided.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray / methods
  • DNA / chemistry*
  • DNA, Cruciform / chemistry
  • Drug Design
  • Intercalating Agents / chemistry
  • Ligands
  • Magnetic Resonance Spectroscopy / methods
  • Models, Chemical
  • Molecular Conformation
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Peptide Nucleic Acids / chemistry
  • Phosphates / chemistry
  • RNA / chemistry
  • Stereoisomerism


  • DNA, Cruciform
  • Intercalating Agents
  • Ligands
  • Oligonucleotides
  • Peptide Nucleic Acids
  • Phosphates
  • RNA
  • DNA