Structural studies of DNA-binding metal complexes of therapeutic importance

Cardin, C. J. ORCID: https://orcid.org/0000-0002-2556-9995 and Hall, J. P. ORCID: https://orcid.org/0000-0003-3716-4378 (2018) Structural studies of DNA-binding metal complexes of therapeutic importance. In: Waring, M. J. (ed.) DNA-targeting Molecules as Therapeutic Agents. Royal Society of Chemistry, pp. 198-227. ISBN 9781782629924 doi: 10.1039/9781788012928-00198

Abstract/Summary

Ruthenium polypyridyl complexes are of interest for their possible applications as cellular probes, in anticancer therapeutics and, most recently, for their antibacterial properties. For many years there was no crystallographic evidence showing how any of these complexes bound to duplex or higher-order DNA, but since 2011 a series of structural studies have shown aspects of sequence, enantiomeric, substituent and structural specificity. The principal binding mode to duplex DNA of complexes typified by [Ru(phen)2dppz]2+ (where dppz=dipyridophenazene) is by angled (canted) intercalation from the minor groove, with a distinct symmetric binding mode so far only known for lambda enantiomers at the TA/TA steps. Kinking (semi-intercalation) has also been characterised, so far only at CC/GG steps, e.g. for phen ligands within these complexes. Delta enantiomers are capable of mismatch recognition, so far structurally characterised for the A–A mismatch. This binding mode, insertion, is characterised by the flipping out of the adenine, with the base stacking on the ancillary ligand of the complex. For binding to higher-order DNA, sequences with loops, such as the unimolecular G-quadruplex, have so far resisted attempts at crystallisation, although an NMR structure of a diruthenium complex has been reported.

Item Type	Book or Report Section
URI	https://reading-clone.eprints-hosting.org/id/eprint/88305
Item Type	Book or Report Section
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	Royal Society of Chemistry
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