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DNA Minor Groove Binding with Bisbenzamidine-Ru(II) Complexes

preprint
submitted on 13.05.2019 and posted on 15.05.2019 by Mateo I. Sánchez, Gustavo Rama, Renata Calo, Kübra Ucar, Per Lincoln, Miguel Vázquez López, Manuel Melle-Franco, José Luis Mascareñas, M. Eugenio Vázquez
We report the first Ru(II) coordination compounds that interact with DNA through a canonical minor groove insertion mode and with selectivity for A/T rich sites. This was made possible by integrating a bis‑benzamidine minor groove DNA-binding agent with a ruthenium(II) complex. Importantly, one of the enantiomers (Δ‑[Ru(bpy)2b4bpy]2+, Δ‑4Ru) shows a considerably higher DNA affinity than the parent organic ligand and than the other enantiomer, particularly for the AATT sequence, while the other enantiomer preferentially targets long AAATTT sites with overall lower affinity. Finally, we demonstrate that the photophysical properties of these new binders can be exploited for DNA cleavage using visible light.

Funding

CTQ2015-70698-R

SAF2016-76689-R

Orfeo-cinqa network CTQ2016-81797-REDC

Xunta de Galicia (2015-CP082, ED431C 2017/19, Centro singular de investigación de Galicia accreditation 2016–2019, ED431G/09)

European Regional Development Fund - ERDF

European Research Council (Advanced Grant No. 340055)

Portuguese Foundation for Science and Technology, FCT, (IF/00894/2015)

CICECO – Aveiro Institute of Materials, FCT Ref. UID/CTM/50011/2019

Fundación Asociación Española Contra el Cáncer (AECC) (IDEAS197VAZQ grant)

History

Email Address of Submitting Author

eugenio.vazquez@usc.es

Institution

Universidade de Santiago de Compostela

Country

Spain

ORCID For Submitting Author

0000-0001-7500-985X

Declaration of Conflict of Interest

No conflict of interests

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