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Angew Chem Int Ed Engl. 2019 Jul 15;58(29):9881-9885. doi: 10.1002/anie.201814502. Epub 2019 Jun 12.

Structural Studies Reveal Enantiospecific Recognition of a DNA G-Quadruplex by a Ruthenium Polypyridyl Complex.

Author information

1
Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK.
2
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, UK.
3
Department of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AH, UK.

Abstract

By using X-ray crystallography, we show that the complexes Λ/Δ-[Ru(TAP)2 (11-CN-dppz)]2+ (TAP=1,4,5,8-tetraazaphenanthrene, dppz=dipyridophenazine) bind DNA G-quadruplex in an enantiospecific manner that parallels the specificity of these complexes with duplex DNA. The Λ complex crystallises with the normally parallel stranded d(TAGGGTTA) tetraplex to give the first such antiparallel strand assembly in which syn-guanosine is adjacent to the complex at the 5' end of the quadruplex core. SRCD measurements confirm that the same conformational switch occurs in solution. The Δ enantiomer, by contrast, is present in the structure but stacked at the ends of the assembly. In addition, we report the structure of Λ-[Ru(phen)2 (11-CN-dppz)]2+ bound to d(TCGGCGCCGA), a duplex-forming sequence, and use both structural models to provide insight into the motif-specific luminescence response of the isostructural phen analogue enantiomers.

KEYWORDS:

DNA recognition; DNA structures; G-quadruplexes; polypyridyl ligands; ruthenium

PMID:
30958918
DOI:
10.1002/anie.201814502

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