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 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 Interaction of TMPyP4, TMPyP3, and TMPyP2 with Intramolecular G-Quadruplex Formed by Promoter Region of Bcl2 and KRAS NHPPE

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Narayana Nagesh ◽  
Arumugam Ganesh Kumar
Keyword(s):  
Promoter Region ◽  
Dna Interaction ◽  
Predominant Role ◽  
Promoter Regions ◽  
Ligand Interaction ◽  
Quadruplex Dna ◽  
Molecular Binding ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Structure Environment

Oncogenes are rich in guanine and capable of forming quadruplex structure. Promoter regions oncogenes such as Bcl2 and KRAS NHPPE are rich in guanine content and they can form quadruplex structures. Alterations in the mode and nature of molecular binding to DNA, certainly has effect on the posttranscriptional activities. Recent experiments indicate that structure of quadruplex complex and ligand has predominant role on ligand-quadruplex DNA interaction. In order to understand the nature of each ligand interaction with quadruplex DNA, Bcl2, KRAS NHPPE quadruplex DNA interaction with three porphyrin was studied using spectroscopy, microcalorimetry and mass spectrometry. Our studies, indicate that mode of ligand interaction varies with structure, environment and concentration of ligand. Fluorescence quenching experiments show that TMPyP4 interaction is ligand concentration dependent. Job plots and ITC experiments demonstrate that four molecules of TMPyP4 and two molecules of TMPyP3, TMPyP2 interact with each quadruplex complex. Through ITC titrations, ligand binding constant are higher for TMPyP4 (≈107 M−1) compared to TMPyP3, TMPyP2 (≈105 M−1). ESI-MS experiments confirm the stoichiometry of TMPyP4 : 39Bcl2 is 4 : 1 at saturation and it is 2 : 1 in case of KRAS NHPPE quadruplex.

scholarly journals G-quadruplex DNA and ligand interaction in living cells using NMR spectroscopy

2015 ◽  
Vol 6 (6) ◽  
pp. 3314-3320 ◽  
Author(s):  
Gilmar F. Salgado ◽  
Christian Cazenave ◽  
Abdelaziz Kerkour ◽  
Jean-Louis Mergny
Keyword(s):  
Nucleic Acid ◽  
Nmr Spectroscopy ◽  
Ligand Binding ◽  
Living Cells ◽  
Ligand Interaction ◽  
Quadruplex Dna ◽  
G Quadruplex

Using in-cell NMR spectroscopy to probe ligand binding to a G-quadruplex nucleic acid.

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 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 Effect of Ionic Strength on Porphyrin Drugs Interaction with Quadruplex DNA Formed by the Promoter Region of C-myc and Bcl2 Oncogenes

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Narayana Nagesh ◽  
Varun K. Sharma ◽  
A. Ganesh Kumar ◽  
Edwin A. Lewis
Keyword(s):  
Ionic Strength ◽  
Fluorescence Spectroscopy ◽  
Drug Interactions ◽  
Promoter Region ◽  
Promoter Regions ◽  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Drugs Interaction ◽  
Dna Complex

C-myc and Bcl2 are well characterized oncogenes that are capable of forming G-quadruplex structures. Promoter regions of C-myc and Bcl2 forming G-quadruplex structures are chemically synthesized and G-quadruplex structure is formed in presence of 100 mM potassium ion. Three different porphyrin drugs, namely TMPyP2, TMPyP3, and TMPyP4 are allowed to interact with quadruplex DNA complex and the site and nature of interaction are studied. Drug interactions with quadruplex DNA were carried out in different potassium ionic strengths using fluorescence spectroscopy. It is found that fluorescence hypochromicity decreases with an increase in ionic strength in the case of TMPyP4, TMPyP3, and TMPyP2. Fluorescence titration studies and Job plots indicate that four molecules of TMPyP4, two molecules of TMPyP3 and TMPyP2 are interacting with one molecule of quadruplex DNA.

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.

Synthesis of phenanthridine spiropyrans and studies of their effects on G-quadruplex DNA

2017 ◽  
Vol 15 (15) ◽  
pp. 3265-3275 ◽  
Author(s):  
M. Livendahl ◽  
J. Jamroskovic ◽  
M. Hedenström ◽  
T. Görlich ◽  
N. Sabouri ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex

Low molecular weight spirocycles efficiently stabilize G-quadruplex DNA without changing its structure by binding the top of the G-quadruplex structure.

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