scholarly journals Probing Ligand and Cation Binding Sites in G-Quadruplex Nucleic Acids by Mass Spectrometry and Electron Photodetachment Dissociation Sequencing

2019 ◽  
Author(s):  
Dababrata Paul ◽  
Adrien Marchand ◽  
Daniela Verga ◽  
Marie-Paule Teulade-Fichou ◽  
Sophie Bombard ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ligand Binding ◽  
Binding Sites ◽  
Binding Mode ◽  
Cation Binding ◽  
Potassium Cation ◽  
Telomeric Sequences ◽  
G Quadruplex ◽  
Electron Photodetachment ◽  
Noncovalent Bonds

ABSTRACTMass spectrometry provides exquisite detail on ligand and cation binding stoichiometries with a DNA target. The next important step is to develop reliable methods to determine the cation and ligand binding sites in each complex separated by the mass spectrometer. To circumvent the caveat of ligand derivatization for cross-linking, which may alter the ligand binding mode, we explored a tandem mass spectrometry (MS/MS) method that does not require ligand derivatization, and is therefore also applicable to localize metal cations. By obtaining more negative charge states for the complexes using supercharging agents, and by creating radical ions by electron photodetachment, oligonucleotide bonds become weaker than the DNA-cation or DNA-ligand noncovalent bonds upon collision-induced dissociation of the radicals. This electron photodetachment (EPD) method allows to locate the binding regions of cations and ligands by top-down sequencing of the oligonucleotide target. The very potent G-quadruplex ligands 360A and PhenDC3 were found to replace a potassium cation and bind close to the central loop of 4-repeat human telomeric sequences.

scholarly journals Probing ligand and cation binding sites in G-quadruplex nucleic acids by mass spectrometry and electron photodetachment dissociation sequencing

The Analyst ◽  
2019 ◽  
Vol 144 (11) ◽  
pp. 3518-3524 ◽  
Author(s):  
Dababrata Paul ◽  
Adrien Marchand ◽  
Daniela Verga ◽  
Marie-Paule Teulade-Fichou ◽  
Sophie Bombard ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Ligand Binding ◽  
Binding Sites ◽  
Cation Binding ◽  
Tandem Mass ◽  
Top Down ◽  
G Quadruplex ◽  
Ligand Binding Sites ◽  
Electron Photodetachment

Tandem mass spectrometry: native top-down sequencing by electron photodetachment dissociation (EPD) reveals ligand binding sites on DNA G-quadruplexes.

scholarly journals What stoichiometries determined by mass spectrometry reveal about the ligand binding mode to G-quadruplex nucleic acids

2017 ◽  
Vol 1861 (5) ◽  
pp. 1353-1361 ◽  
Author(s):  
Michael J. Lecours ◽  
Adrien Marchand ◽  
Ahdia Anwar ◽  
Corinne Guetta ◽  
W. Scott Hopkins ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Nucleic Acids ◽  
Ligand Binding ◽  
Binding Mode ◽  
G Quadruplex

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

2020 ◽  
Author(s):  
Michael O'Hagan ◽  
Javier Ramos Soriano ◽  
Susanta Haldar ◽  
Juan Carlos Morales ◽  
Adrian Mulholland ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Visible Light ◽  
Uv Light ◽  
Binding Mode ◽  
High Energy ◽  
Light Sources ◽  
Biologically Relevant ◽  
G Quadruplex ◽  
Potential Applications ◽  
Robust Regulation

<div><p>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.</p></div><br>

scholarly journals Visible-light photoswitching of ligand binding mode suggests G-quadruplex DNA as a target for photopharmacology

2020 ◽  
Vol 56 (38) ◽  
pp. 5186-5189 ◽  
Author(s):  
Michael P. O’Hagan ◽  
Javier Ramos-Soriano ◽  
Susanta Haldar ◽  
Sadiyah Sheikh ◽  
Juan C. Morales ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Visible Light ◽  
Binding Mode ◽  
Quadruplex Dna ◽  
G Quadruplex

A pyridinium-decorated photoresponsive dithienylethene selectively targets G-quadruplex DNA, allowing binding mode and toxicity to be controlled exclusively with visible light.

Analysis of experimental binding curves of EtBr with single- and double-stranded DNA at small fillings

2014 ◽  
Vol 28 (22) ◽  
pp. 1450178 ◽  
Author(s):  
Poghos O. Vardevanyan ◽  
Valeri B. Arakelyan ◽  
Marine A. Parsadanyan ◽  
Ara P. Antonyan ◽  
Gohar G. Hovhannisyan ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Sites ◽  
Binding Mode ◽  
Ligand Molecule ◽  
Binding Parameters ◽  
Base Pairs ◽  
Precise Data ◽  
Double Stranded Dna ◽  
Single Curve ◽  
Binding Curves

In this paper, a method that allows to analyze the binding curves of ligand ( EtBr ) with single-stranded (ss) and double-stranded (ds) DNA, when there are at least two modes of ligand binding to DNA at small fillings has been proposed. The obtained experimental binding curves for EtBr –ssDNA and EtBr –dsDNA have two clearly expressed linear regions. These curves were analyzed by two modes: Experimental points on linear regions were described by two different lines and all experimental points were described by single curve. It was revealed that the description by single curve permits obtaining more precise data of binding parameters (i.e. binding constant and number of base pairs that bind one ligand molecule). Moreover, the proposed method permits determining the value of proportion of binding sites of each binding mode.

Epitope Ligand Binding Sites of Blood Group Oligosaccharides in Lectins Revealed by Pressure-Assisted Proteolytic Excision Affinity Mass Spectrometry

2018 ◽  
Vol 29 (9) ◽  
pp. 1881-1891 ◽  
Author(s):  
Yannick Baschung ◽  
Loredana Lupu ◽  
Adrian Moise ◽  
Michael Glocker ◽  
Stephan Rawer ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ligand Binding ◽  
Blood Group ◽  
Binding Sites ◽  
Ligand Binding Sites

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

2020 ◽  
Author(s):  
Michael O'Hagan ◽  
Javier Ramos Soriano ◽  
Susanta Haldar ◽  
Juan Carlos Morales ◽  
Adrian Mulholland ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Visible Light ◽  
Uv Light ◽  
Binding Mode ◽  
High Energy ◽  
Light Sources ◽  
Biologically Relevant ◽  
G Quadruplex ◽  
Potential Applications ◽  
Robust Regulation

<div><p>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.</p></div><br>

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

2020 ◽  
Author(s):  
Michael O'Hagan ◽  
Javier Ramos Soriano ◽  
Susanta Haldar ◽  
Juan Carlos Morales ◽  
Adrian Mulholland ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Visible Light ◽  
Uv Light ◽  
Binding Mode ◽  
High Energy ◽  
Light Sources ◽  
Biologically Relevant ◽  
G Quadruplex ◽  
Potential Applications ◽  
Robust Regulation

<div><p>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.</p></div><br>

scholarly journals DNA and RNA Telomeric G-Quadruplexes: What Topology Features Can be Inferred from Ion Mobility Mass Spectrometry?

2019 ◽  
Author(s):  
Valentina D’Atri ◽  
Valerie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Ion Mobility Spectrometry ◽  
Ion Mobility ◽  
Native Mass Spectrometry ◽  
Cation Binding ◽  
Telomeric Dna ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Multiple Structures

Maintenance of the telomeres is key to chromosome integrity and cell proliferation. The G-quadruplex structures formed by telomeric DNA and RNA (TTAGGG and UUAGGG repeats, respectively) are key to this process. However, because these sequences are particularly polymorphic, solving high-resolution structures is not always possible, and there is a need for new methodologies to characterize the multiple structures coexisting in solution. In this context, we evaluated whether ion mobility spectrometry coupled to native mass spectrometry could help separate and assign the G-quadruplex topologies. We explored the circular dichroism spectra, multimer formation, cation binding, and ion mobility spectra of several 4-repeat and 8-repeat telomeric DNA and RNA sequences, both in NH<sub>4</sub><sup>+</sup> and in K<sup>+</sup>. In 1 mM K<sup>+</sup> and 100 mM trimethylammonium acetate, all RNAs fold intramolecularly (no multimer). In 8-repeat sequences, the subunits are not independent: in DNA the first subunit disfavors the folding of the second one, whereas in RNA the two subunits fold cooperatively via cation-mediated stacking. Ion mobility spectrometry shows that gas-phase structures keep a memory of the solution ones, but not identical. At the native charge states, the loops can rearrange in a variety of ways (unless they are constrained by pre-formed hydrogen bonds), thereby wrapping the core and masking the strand arrangements. Our study highlights that, to progress towards structural assignment from IM-MS experiments, deeper understanding of the solution-to-gas-phase rearrangement mechanisms is warranted. <br>

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