scholarly journals Direct evidence of mitochondrial G-quadruplex DNA by using fluorescent anti-cancer agents

2015 ◽  
pp. gkv1061 ◽  
Author(s):  
Wei-Chun Huang ◽  
Ting-Yuan Tseng ◽  
Ying-Ting Chen ◽  
Cheng-Chung Chang ◽  
Zi-Fu Wang ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Quadruplex Dna ◽  
Anti Cancer ◽  
G Quadruplex

Targeting G-quadruplex DNA as Potential Anti-cancer Therapy

2017 ◽  
pp. 129-162
Author(s):  
Riccardo Bonsignore ◽  
Elisa Trippodo ◽  
Giampaolo Barone
Keyword(s):  
Cancer Therapy ◽  
Quadruplex Dna ◽  
Anti Cancer ◽  
G Quadruplex

Molecular recognition of parallel quadruplex [d-(TTGGGGT)]4 by mitoxantrone: binding with 1 : 4 stoichiometry leads to telomerase inhibition

RSC Advances ◽  
2016 ◽  
Vol 6 (75) ◽  
pp. 71652-71661 ◽  
Author(s):  
Tarikere Palakshan Pradeep ◽  
Sweta Tripathi ◽  
Ritu Barthwal
Keyword(s):  
Molecular Recognition ◽  
Thermal Stabilization ◽  
Cancer Drug ◽  
Telomerase Inhibition ◽  
Quadruplex Dna ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Cd Studies

NMR and CD studies show that anti-cancer drug mitoxantrone (MTX) binds to parallel G-quadruplex DNA [d-(TTGGGGT)4] as stacked dimer at grooves leading to increase in thermal stabilization of DNA by ~25 °C and inhibits telomerase with IC50 = 2 μM.

scholarly journals High throughput screening of a new fluorescent G-quadruplex ligand having telomerase inhibitory activity in human A549 cells

2021 ◽  
Author(s):  
Sourav Ghosh ◽  
Debapriya De ◽  
Victor Banerjee ◽  
Soumyajit Biswas ◽  
Utpal Ghosh
Keyword(s):  
Dna Sequences ◽  
High Throughput Screening ◽  
A549 Cells ◽  
Telomerase Activity ◽  
Live Cells ◽  
Cancer Drug ◽  
Quadruplex Dna ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Human A549

Genome-wide analysis showed that putative G-quadruplex DNA structures are prevalent in the human genome. The presence of G-quadruplex structure in the telomere and promoter region of certain oncogenes inspired people to use G-quadruplex ligand as anti-cancer agents. G-quadruplex structures, stabilized by ligand at telomere are resolved by telomerase making the cancer cells resistant to G-quadruplex ligand. So, identification of a new G-quadruplex ligand having anti-telomerase activity would be a promising strategy for cancer therapy as about 85% of human cancers are telomerase positive. A set of the drug-like compounds were screened from the ZINC database randomly and 2284 ligands were chosen following Lipinski rule of five that were docked with five different G-quadruplex DNA sequences in idock. We screened 43 potential G-quadruplex binders using Z-score as a normalization scoring function. The compound (ZINC ID- 05220992) gave the best score (average idock = -10.17 kcal/mol, average normalized idock = -3.42). We performed G4 FID assay, CD analysis to understand its binding with three different G-quadruplex DNA sequences, and checked its anti-telomerase activity in A549 cells using TRAP assay. We observed that this compound had an intrinsic fluorescence, capability to stain live cells with a blue fluorescence, and a specific affinity to only 22AG out of three different G-quadruplex DNA sequences under study. It showed cytotoxicity, good permeability to live cells, and a significant reduction of telomerase activity in human A549 cells at a very low dose. So, this compound has strong potential to be an anti-cancer drug.

scholarly journals G-QUADRUPLEX LIGANDS AS STABILIZER TARGETING TELOMERASE ENZYME AS ANTI CANCER AGENTS

2017 ◽  
Vol 10 (8) ◽  
pp. 50
Author(s):  
Hemalatha Cn ◽  
Vijey Aanandhi M ◽  
Vijey Aanandhi M
Keyword(s):  
Basic Research ◽  
The Novel ◽  
Telomeric Dna ◽  
Inhibitor Activity ◽  
Quadruplex Dna ◽  
Biological Studies ◽  
Anti Cancer ◽  
G Quadruplex ◽  
Biophysical Studies ◽  
Lagging Strand

The human telomere stabilization with G-Quadruplex DNA tends to induce apoptosis. The molecular target of telomere cascade with a rigid molecular may show efficacious to treat cancer. The study of intercalation to human telomeric DNA with proposed ligand can be evaluated by the help of biophysical studies and biological studies. G-Quadruplex is one of the key epigenetic episodes of eukaryotes and prokaryotes, generally found in the telomeric end region, immunoglobulin switch recombination and the lagging strand of the DNA. These chemotherapeutic advances are not enough to maintain a life expectancy of cancer affected patients. A number of G-Quadruplex ligands such as acridine, perylene, and anthraquinones have been synthesized reported and evaluated them for the inhibitor activity. Therefore, translational research can pave the novel prospect to treat cancer in a fundamental way. In that connection, basic research showed G-Quadruplex phenomenon of DNA, which is having a great impact in this chemotherapy.

Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

2020 ◽  
Vol 27 (1) ◽  
pp. 154-169 ◽  
Author(s):  
Claudiu N. Lungu ◽  
Bogdan Ionel Bratanovici ◽  
Maria Mirabela Grigore ◽  
Vasilichia Antoci ◽  
Ionel I. Mangalagiu
Keyword(s):  
Experimental Data ◽  
Antimicrobial Properties ◽  
Qsar Model ◽  
Therapeutic Effectiveness ◽  
Computational Results ◽  
Pyridine Derivatives ◽  
Quadruplex Dna ◽  
Dna Intercalators ◽  
Structure Activity ◽  
G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

Emerging Role of G-quadruplex DNA as Target in Anticancer Therapy

2017 ◽  
Vol 22 (44) ◽  
pp. 6612-6624 ◽  
Author(s):  
Graziella Cimino-Reale ◽  
Nadia Zaffaroni ◽  
Marco Folini
Keyword(s):  
Anticancer Therapy ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus

2021 ◽  
Vol 22 (5) ◽  
pp. 2409
Author(s):  
Anastasia A. Bizyaeva ◽  
Dmitry A. Bunin ◽  
Valeria L. Moiseenko ◽  
Alexandra S. Gambaryan ◽  
Sonja Balk ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Core Structure ◽  
Dna Aptamer ◽  
Tertiary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Flanking Sequences ◽  
Related Proteins

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.

scholarly journals DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions

2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Drug Targets ◽  
Native Mass Spectrometry ◽  
Drug Binding ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Nmr Structures ◽  
G Quadruplex ◽  
Screening Assays

Abstract G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).

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