Screening of DNA G-quadruplex stabilizing ligands by nano differential scanning fluorimetry

The Analyst ◽  
2019 ◽  
Vol 144 (22) ◽  
pp. 6512-6516 ◽  
Author(s):  
Bruno Pagano ◽  
Nunzia Iaccarino ◽  
Anna Di Porzio ◽  
Antonio Randazzo ◽  
Jussara Amato
Keyword(s):  
Screening Tool ◽  
G Quadruplex ◽  
Differential Scanning Fluorimetry ◽  
Stabilizing Ligands ◽  
Proof Of Principle

A proof of principle study on the use of nanoDSF as a screening tool for G-quadruplex targeting compounds.

scholarly journals Naphthalenediimide-Linked Bisbenzimidazole Derivatives as Telomeric G-Quadruplex-Stabilizing Ligands with Improved Anticancer Activity

ACS Omega ◽  
2017 ◽  
Vol 2 (3) ◽  
pp. 966-980 ◽  
Author(s):  
Souvik Sur ◽  
Vinod Tiwari ◽  
Devapriya Sinha ◽  
Mohammad Zahid Kamran ◽  
Kshatresh Dutta Dubey ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
G Quadruplex ◽  
Stabilizing Ligands

scholarly journals G4-Selective Ligand Induced Autophagy

2021 ◽  
Author(s):  
Piyali Majumder ◽  
Chinmayee Shukla ◽  
Bhaskar Datta
Keyword(s):  
Gene Regulation ◽  
Negative Regulator ◽  
Homeostatic Mechanism ◽  
Selective Ligand ◽  
Carbocyanine Dye ◽  
G Quadruplex ◽  
Selective Ligands ◽  
Functional Context ◽  
Stabilizing Ligands ◽  
Mtor Activity

G-quadruplex (G4) structures have emerged as singular therapeutic targets for cancer and neurodegeneration. Autophagy is a housekeeping cellular homeostatic mechanism and deregulation of autophagy is common in cancer and in neurodegenerative diseases. In this study, we identified the presence of 46 putative G4 sequences in the MTOR gene by use of QGRS mapper tool. We sought to connect these putative G4 sequences to a functional context by leveraging G4-targeting ligands. A G4-selective dimeric carbocyanine dye Bis-4,3 and the porphyrin TMPyP4 were used to affect the replication, transcription and translation of the MTOR gene. The ligand-induced induction of autophagic pathway via MTOR gene regulation was monitored upon treatment of HeLa and SHSY-5Y cells with G4-targeting ligands. The use of Bis-4,3 was compared with the known G4-stabilizing activity of TMPyP4. Our results show that treatment with G4-selective ligands downregulates mTOR activity and leads to the induction of excessive autophagy. This is first report on effect of G4-selective ligands on MTOR regulation and mTOR expression. mTOR being the key negative regulator of autophagy, the current work suggests potential of G4 stabilizing ligands towards induction of autophagy through the downregulation of mTOR.

scholarly journals Discovery of G-quadruplex stabilizing ligands through direct ELISA of a one-bead-one-compound library

2006 ◽  
Vol 4 (23) ◽  
pp. 4364 ◽  
Author(s):  
James E. Redman ◽  
Sylvain Ladame ◽  
Anthony P. Reszka ◽  
Stephen Neidle ◽  
Shankar Balasubramanian
Keyword(s):  
Compound Library ◽  
G Quadruplex ◽  
Direct Elisa ◽  
Stabilizing Ligands

Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands

2015 ◽  
Vol 55 (10) ◽  
pp. 2094-2110 ◽  
Author(s):  
Daimel Castillo-González ◽  
Jean-Louis Mergny ◽  
Aurore De Rache ◽  
Gisselle Pérez-Machado ◽  
Miguel Angel Cabrera-Pérez ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Best Practices ◽  
Screening Tool ◽  
G Quadruplex

Enhancement Effect of Zn-Arsenazo III Complex for G-quadruplex DNA Stability of Proto-oncogene Promoter Telomeres

2020 ◽  
Vol 17 (7) ◽  
pp. 858-866
Author(s):  
Liyuan Zou ◽  
Hongbo Li ◽  
Mingbin Liu ◽  
Weihua Zhao ◽  
Suqin Wang
Keyword(s):  
Enhancement Effect ◽  
Antitumor Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Cellular Context ◽  
Different Temperatures ◽  
Nucleic Acid Stain ◽  
Reciprocal Method ◽  
Growth Of Tumor ◽  
Stabilizing Ligands

Background: Controlling the structure of proto-oncogene telomeres is very important in antitumor therapy. There are relationships between G-quadruplex DNA and the growth of tumor cell. Methods: In this study, spectroscopic, cyclic voltammetry and viscosity methods were employed to investigate the interaction between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA by using 4S Green Plus Nucleic Acid Stain as a spectral probe in PBS buffer. The binding ratios were n Arsenazo Ⅲ : n Zn(Ⅱ) = 5:1 for Zn-Arsenazo Ⅲ complex and n Zn- Arsenazo Ⅲ : n G-quadruplex DNA = 8:1 for Zn-Arsenazo Ⅲ-G-quadruplex DNA. The bonding constants (Kθ 298.15K=4.44x105 L·mol-1, Kθ 308.15K= 1.00x105 L·mol-1, Kθ 318.15K= 1.04x106 L·mol-1) were obtained by double reciprocal method at different temperatures, Which was found that the interaction between Zn-Arsenazo Ⅲ complex and Gquadruplex DNA was driven by enthalpy. Furthermore, the research further confirmed that the interaction mode between Zn-Arsenazo Ⅲ complex and G-quadruplex DNA was a mixed binding which involved intercalation and non-intercalation interaction. Results and Conclusion: Together these findings also have corroborated the application of stabilizing ligands and intervening with their function for target G-quadruplexes in a cellular context.

scholarly journals Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

Molecules ◽  
2013 ◽  
Vol 18 (11) ◽  
pp. 13446-13470 ◽  
Author(s):  
Alessandro Altieri ◽  
Antonello Alvino ◽  
Stephan Ohnmacht ◽  
Giancarlo Ortaggi ◽  
Stephen Neidle ◽  
...  
Keyword(s):  
Xanthone Derivatives ◽  
G Quadruplex ◽  
Stabilizing Ligands

Tetramethylpyridiniumporphyrazines — A New Class of G-Quadruplex Inducing and Stabilizing Ligands.

ChemInform ◽  
2007 ◽  
Vol 38 (10) ◽  
Author(s):  
Diana P. N. Goncalves ◽  
Raphael Rodriguez ◽  
Shankar Balasubramanian ◽  
Jeremy K. M. Sanders
Keyword(s):  
New Class ◽  
G Quadruplex ◽  
Stabilizing Ligands

scholarly journals Control of the polyamine biosynthesis pathway by G2-quadruplexes

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Helen Louise Lightfoot ◽  
Timo Hagen ◽  
Antoine Cléry ◽  
Frédéric Hai-Trieu Allain ◽  
Jonathan Hall
Keyword(s):  
Feedback Loops ◽  
Polyamine Biosynthesis ◽  
Biophysical Characterization ◽  
Cellular Assays ◽  
Naturally Occurring ◽  
Genome Wide ◽  
G Quadruplex ◽  
Stabilizing Ligands ◽  
Influence Gene Expression

G-quadruplexes are naturally-occurring structures found in RNAs and DNAs. Regular RNA G-quadruplexes are highly stable due to stacked planar arrangements connected by short loops. However, reports of irregular quadruplex structures are increasing and recent genome-wide studies suggest that they influence gene expression. We have investigated a grouping of G2-motifs in the UTRs of eight genes involved in polyamine biosynthesis, and concluded that several likely form novel metastable RNA G-quadruplexes. We performed a comprehensive biophysical characterization of their properties, comparing them to a reference G-quadruplex. Using cellular assays, together with polyamine-depleting and quadruplex-stabilizing ligands, we discovered how some of these motifs regulate and sense polyamine levels, creating feedback loops during polyamine biosynthesis. Using high-resolution 1H-NMR spectroscopy, we demonstrated that a long-looped quadruplex in the AZIN1 mRNA co-exists in salt-dependent equilibria with a hairpin structure. This study expands the repertoire of regulatory G-quadruplexes and demonstrates how they act in unison to control metabolite homeostasis.

scholarly journals Molecular docking based screening of triterpenoids as potential G-quadruplex stabilizing ligands with anti-cancer activity

2017 ◽  
Vol 13 (09) ◽  
pp. 284-292 ◽  
Author(s):  
Sittichai Sillapapongwarakorn ◽  
◽  
Somchai Yanarojana ◽  
Darawan Pinthong ◽  
Amnuay Thithapandha ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Stabilizing Ligands ◽  
Cancer Activity
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