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Visible-Light Photoswitching of G-Quadruplex Ligand Binding Mode Allows Reversible Control of G-Tetrad Structure

preprint
revised on 13.02.2020 and posted on 14.02.2020 by Michael O'Hagan, Javier Ramos Soriano, Susanta Haldar, Juan Carlos Morales, Adrian Mulholland, M. Carmen Galan

Photoresponsive ligands for G-quadruplex oligonucleotides (G4) offer exciting opportunities for the reversible regulation of these assemblies with potential applications in biological chemistry and responsive nanotechnology. However, achieving the robust regulation of G4 ligand activity with low-energy visible light sources that are easily accessible and compatible with biological systems remains a significant challenge to realizing these applications. Herein, we report the G4-binding properties of a photoresponsive dithienylethene (DTE). We demonstrate the first example of G4-specific acceleration of the photoswitching kinetics of a small molecule and the visible-light mediated switching of the G4 ligand binding mode in physiologically-relevant conditions, which in turn allows control over the G4 tetrad structure of telomeric G4 in potassium buffer. The process is fully reversible and avoids the need for high-energy UV light. This affords an efficient, practical and biologically-relevant means of control that may be applied in the generation of new responsive G4/ligand supramolecular systems.


Funding

EPSRC Centre for Doctoral Training in Chemical Synthesis

Engineering and Physical Sciences Research Council

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European Research Council (ERC-COG: 648239).

EPSRC EP/M015378/1 and EP/M022609/1].

Spanish Ministerio de Economía y Competitividad (Grant CTQ2015-64275-P and RTI2018-099036-B-I00).

History

Email Address of Submitting Author

m.c.galan@bristol.ac.uk

Institution

School of Chemistry, University of Bristol, Bristol, BS8 1TS

Country

United Kingdom

ORCID For Submitting Author

0000-0001-7307-2871

Declaration of Conflict of Interest

No conflict of interests

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