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Structural studies reveal the enantiospecific recognition of a DNA G-quadruplex by a ruthenium polypyridyl complex

DOI: 10.1002/anie.201814502 DOI Help

Authors: Kane Mcquaid (University of Reading) , Holly Abell (University of Reading) , Sarah Gurung (University of Reading) , David Allan (Diamond Light Source) , Graeme Winter (Diamond Light Source) , Thomas Sorensen (Diamond Light Source) , David J. Cardin (University of Reading) , John Brazier (University of Reading) , Christine J. Cardin (University of Reading) , James P. Hall (University of Reading)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Angewandte Chemie International Edition

State: Published (Approved)
Published: April 2019
Diamond Proposal Number(s): 14493 , 14916 , 15733

Abstract: Using X‐ray crystallography, we show an enantiospecificity in DNA G‐quadruplex binding, using the complexes Λ/∆‐[Ru(TAP)2(dppz‐11‐CN)]2+ (TAP=1,4,5,8‐tetraazaphenanthrene) containing the dppz (dipyridophenazine) ligand, paralleling the specificity of the 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 aid in the elucidation of the motif‐specific luminescence response of the isostructural phen analogue enantiomers.

Journal Keywords: G-quadruplex; Ruthenium polypyridyl; X-ray crystallography; Enantiospecificity; ‘Light-switch'

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: B23-Circular Dichroism , I02-Macromolecular Crystallography