Probing a major DNA weakness: resolving the groove and sequence selectivity of the diimine complex Λ‐[Ru(phen)2phi]2+

Prieto Otoya, T. D., McQuaid, K. T. ORCID: https://orcid.org/0000-0002-3222-5584, Hennessy, J., Menounou, G., Gibney, A., Paterson, N., Cardin, D. J., Kellett, A. and Cardin, C. J. ORCID: https://orcid.org/0000-0002-2556-9995 (2024) Probing a major DNA weakness: resolving the groove and sequence selectivity of the diimine complex Λ‐[Ru(phen)2phi]2+. Angewandte Chemie International Edition. ISSN 1521-3773 doi: 10.1002/anie.202318863

Abstract/Summary

The grooves of DNA provide recognition sites for many nucleic acid binding proteins and anticancer drugs such as the covalently binding cisplatin. Here we report a crystal structure showing, for the first time, groove selectivity by an intercalating ruthenium complex. The complex Λ‐[Ru(phen)2phi]2+, where phi = 9,10‐phenanthrenediimine, is bound to the DNA decamer duplex d(CCGGTACCGG)2. The structure shows that the metal complex is symmetrically bound in the major groove at the central TA/TA step, and asymmetrically bound in the minor groove at the adjacent GG/CC steps. A third type of binding links the strands, in which each terminal cytosine base stacks with one phen ligand. The overall binding stoichiometry is four Ru complexes per duplex. Complementary biophysical measurements confirm the binding preference for the Λ‐enantiomer and show a high affinity for TA/TA steps and, more generally, TA‐rich sequences. A striking enantiospecific elevation of melting temperatures is found for oligonucleotides which include the TATA box sequence.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/115088
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Uncontrolled Keywords	General Chemistry, Catalysis
Publisher	Wiley
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