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.

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 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>

Understanding Ligand Interaction with Different Structures of G-Quadruplex DNA: Evidence of Kinetically Controlled Ligand Binding and Binding-Mode Assisted Quadruplex Structure Alteration

2012 ◽  
Vol 84 (16) ◽  
pp. 7218-7226 ◽  
Author(s):  
Sachin Dev Verma ◽  
Nibedita Pal ◽  
Moirangthem Kiran Singh ◽  
Him Shweta ◽  
Mohammad Firoz Khan ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Mode ◽  
Ligand Interaction ◽  
Quadruplex Dna ◽  
Dna Evidence ◽  
Quadruplex Structure ◽  
Kinetically Controlled ◽  
G Quadruplex

scholarly journals NovelFeIIandCoIIComplexes of Natural Product Tryptanthrin: Synthesis and Binding with G-Quadruplex DNA

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Yi-ning Zhong ◽  
Yan Zhang ◽  
Yun-qiong Gu ◽  
Shi-yun Wu ◽  
Wen-ying Shen ◽  
...  
Keyword(s):  
Natural Products ◽  
Ligand Binding ◽  
Single Crystal ◽  
Natural Product ◽  
Significant Interaction ◽  
Rational Design ◽  
X Ray Diffraction ◽  
Quadruplex Dna ◽  
X Ray ◽  
G Quadruplex

Tryptanthrin is one of the most important members of indoloquinoline alkaloids. We obtained this alkaloid fromIsatis. Two novelFeIIandCoIIcomplexes of tryptanthrin were first synthesized. Single-crystal X-ray diffraction analyses show that these complexes display distorted four-coordinated tetrahedron geometry via two heterocyclic nitrogen and oxygen atoms from tryptanthrin ligand. Binding with G-quadruplex DNA properties revealed that both complexes were found to exhibit significant interaction with G-quadruplex DNA. This study may potentially serve as the basis of future rational design of metal-based drugs from natural products that target the G-quadruplex DNA.

scholarly journals Cation Involvement in Telomestatin Binding to G-Quadruplex DNA

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Frédéric Rosu ◽  
Valérie Gabelica ◽  
Nicolas Smargiasso ◽  
Gabriel Mazzucchelli ◽  
Kazuo Shin-Ya ◽  
...  
Keyword(s):  
Density Functional ◽  
Rational Design ◽  
Density Functional Theory Calculations ◽  
Binding Mode ◽  
Monovalent Cation ◽  
Ammonium Ion ◽  
Mass Measurements ◽  
Functional Theory ◽  
Quadruplex Dna ◽  
G Quadruplex

The binding mode of telomestatin to G-quadruplex DNA has been investigated using electrospray mass spectrometry, by detecting the intact complexes formed in ammonium acetate. The mass measurements show the incorporation of one extra ammonium ion in the telomestatin complexes. Experiments on telomestatin alone also show that the telomestatin alone is able to coordinate cations in a similar way as a crown ether. Finally, density functional theory calculations suggest that in the G-quadruplex-telomestatin complex, potassium or ammonium cations are located between the telomestatin and a G-quartet. This study underlines that monovalent cation coordination capabilities should be integrated in the rational design of G-quadruplex binding ligands.

scholarly journals 9,10-Bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene: Synthesis and G-quadruplex Selectivity

Molbank ◽  
10.3390/m1138 ◽  
2020 ◽  
Vol 2020 (2) ◽  
pp. M1138
Author(s):  
Giovanni Ribaudo ◽  
Alberto Ongaro ◽  
Erika Oselladore ◽  
Giuseppe Zagotto ◽  
Maurizio Memo ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Binding Mode ◽  
Sonogashira Reaction ◽  
Ionization Mass ◽  
Quadruplex Dna ◽  
Anthracene Derivative ◽  
Double Stranded Dna ◽  
G Quadruplex ◽  
A3 Coupling ◽  
Hydroxyethyl Piperazine

G-quadruplex DNA is the target of several natural and synthetic small molecules with antiproliferative and antiviral activity. We here report the synthesis through Sonogashira reaction and A3 coupling of a disubstituted anthracene derivative, 9,10-bis[(4-(2-hydroxyethyl)piperazine-1-yl)prop-2-yne-1-yl]anthracene. The binding of this compound to G-quadruplex and double stranded DNA sequences was evaluated using electrospray ionization mass spectrometry (ESI-MS), demonstrating selectivity for the first structure. The interaction pattern of the ligand with G-quadruplex was investigated by molecular docking and stacking was found to be the preferred binding mode.

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.

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