A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA

Michael O'Hagan; Susanta Haldar; Marta Duchi; Thomas A. A. Oliver; Adrian Mulholland; Juan C Morales; Carmen Galan

doi:10.1002/anie.201900740

A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA

Michael O'Hagan, Susanta Haldar, Marta Duchi, Thomas A. A. Oliver, Adrian Mulholland, Juan C Morales, Carmen Galan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

12 Citations (Scopus)

54 Downloads (Pure)

Abstract

The polymorphic nature of G-quadruplex (G4) DNA structures points to a range of potential applications in nanodevices and an opportunity to control G4 in biological settings. Light is an attractive means for the regulation of oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards the development of ligands for G4 that allow photoregulation of G4 folding. We report a novel G4-binding chemotype derived from stiff-stilbene. Surprisingly however, whilst the ligand induces high stabilization in the potassium form of human telomeric DNA, it causes the unfolding of the same G4 sequence in sodium buffer. This effect can be reversed on demand by irradiation with 400 nm light through deactivation of the ligand by photo-oxidation. By fuelling the system with the photolabile ligand, the conformation of G4 DNA was switched five times.

Original language	English
Pages (from-to)	4334-4338
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	58
Issue number	13
Early online date	20 Feb 2019
DOIs	https://doi.org/10.1002/anie.201900740
Publication status	Published - 22 Mar 2019

Structured keywords

BCS and TECS CDTs

Keywords

circular dichroism
DNA
G-quadruplexes
oligonucleotides
photoregulation

Access to Document

10.1002/anie.201900740

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://doi.org/10.1002/anie.201900740 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 646 KBLicence: Other

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1 Active
2 Finished

Elucidation of energy and charge transportation mechanisms in biomolecules and nanomaterials
Oliver, T.
1/12/17 → 31/03/21
Project: Research
Exploring Delocalised Energy Transport in Bacterial Reaction Centres
Oliver, T.
1/02/17 → 31/07/18
Project: Research
Predicting drug-target binding kinetics through multiscale simulations
Mulholland, A. J.
1/05/15 → 30/04/19
Project: Research

Professor M C Galan
- M.C.Galan@bristol.ac.uk
- School of Chemistry - Professor of Organic and Biological Chemistry
- Synthesis
- Catalysis
- Biological and Archaeological Chemistry
Person: Academic , Member
Professor Adrian J Mulholland
- Adrian.Mulholland@bristol.ac.uk
Person: Academic , Member

Cite this

@article{13a0f3e3f53745e1875fc6201ab04850,

title = "A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA",

abstract = "The polymorphic nature of G-quadruplex (G4) DNA structures points to a range of potential applications in nanodevices and an opportunity to control G4 in biological settings. Light is an attractive means for the regulation of oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards the development of ligands for G4 that allow photoregulation of G4 folding. We report a novel G4-binding chemotype derived from stiff-stilbene. Surprisingly however, whilst the ligand induces high stabilization in the potassium form of human telomeric DNA, it causes the unfolding of the same G4 sequence in sodium buffer. This effect can be reversed on demand by irradiation with 400 nm light through deactivation of the ligand by photo-oxidation. By fuelling the system with the photolabile ligand, the conformation of G4 DNA was switched five times.",

keywords = "circular dichroism, DNA, G-quadruplexes, oligonucleotides, photoregulation",

author = "Michael O'Hagan and Susanta Haldar and Marta Duchi and Oliver, {Thomas A. A.} and Adrian Mulholland and Morales, {Juan C} and Carmen Galan",

year = "2019",

month = mar,

day = "22",

doi = "10.1002/anie.201900740",

language = "English",

volume = "58",

pages = "4334--4338",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "Wiley-VCH Verlag",

number = "13",

}

A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA. / O'Hagan, Michael ; Haldar, Susanta ; Duchi, Marta ; Oliver, Thomas A. A.; Mulholland, Adrian; Morales, Juan C; Galan, Carmen.

In: Angewandte Chemie - International Edition, Vol. 58, No. 13, 22.03.2019, p. 4334-4338.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA

AU - O'Hagan, Michael

AU - Haldar, Susanta

AU - Duchi, Marta

AU - Oliver, Thomas A. A.

AU - Mulholland, Adrian

AU - Morales, Juan C

AU - Galan, Carmen

PY - 2019/3/22

Y1 - 2019/3/22

N2 - The polymorphic nature of G-quadruplex (G4) DNA structures points to a range of potential applications in nanodevices and an opportunity to control G4 in biological settings. Light is an attractive means for the regulation of oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards the development of ligands for G4 that allow photoregulation of G4 folding. We report a novel G4-binding chemotype derived from stiff-stilbene. Surprisingly however, whilst the ligand induces high stabilization in the potassium form of human telomeric DNA, it causes the unfolding of the same G4 sequence in sodium buffer. This effect can be reversed on demand by irradiation with 400 nm light through deactivation of the ligand by photo-oxidation. By fuelling the system with the photolabile ligand, the conformation of G4 DNA was switched five times.

AB - The polymorphic nature of G-quadruplex (G4) DNA structures points to a range of potential applications in nanodevices and an opportunity to control G4 in biological settings. Light is an attractive means for the regulation of oligonucleotide structure as it can be delivered with high spatiotemporal precision. However, surprisingly little attention has been devoted towards the development of ligands for G4 that allow photoregulation of G4 folding. We report a novel G4-binding chemotype derived from stiff-stilbene. Surprisingly however, whilst the ligand induces high stabilization in the potassium form of human telomeric DNA, it causes the unfolding of the same G4 sequence in sodium buffer. This effect can be reversed on demand by irradiation with 400 nm light through deactivation of the ligand by photo-oxidation. By fuelling the system with the photolabile ligand, the conformation of G4 DNA was switched five times.

KW - circular dichroism

KW - DNA

KW - G-quadruplexes

KW - oligonucleotides

KW - photoregulation

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U2 - 10.1002/anie.201900740

DO - 10.1002/anie.201900740

M3 - Article (Academic Journal)

C2 - 30682233

VL - 58

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EP - 4338

JO - Angewandte Chemie - International Edition

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SN - 1433-7851

IS - 13

ER -

A Photoresponsive Stiff-Stilbene Ligand Fuels the Reversible Unfolding of G-Quadruplex DNA

Abstract

Structured keywords

Keywords

Access to Document

Elucidation of energy and charge transportation mechanisms in biomolecules and nanomaterials

Exploring Delocalised Energy Transport in Bacterial Reaction Centres

Predicting drug-target binding kinetics through multiscale simulations

Professor M C Galan

Professor Adrian J Mulholland

Cite this