Multicarbazole scaffolds for selective G-quadruplex binding

2018 ◽  
Vol 54 (69) ◽  
pp. 9647-9650 ◽  
Author(s):  
Arnold Ou ◽  
Aurore Guédin ◽  
Brian W. Skelton ◽  
Samir Amrane ◽  
Cameron W. Evans ◽  
...  
Keyword(s):  
Duplex Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

N-Functionalised multicarbazoles were found to be highly selective towards G-quadruplex DNA in the presence of 250× excess duplex DNA competitor.

Benzofuroquinoline Derivatives Had Remarkable Improvement of their Selectivity for Telomeric G-Quadruplex DNA over Duplex DNA upon Introduction of Peptidyl Group

2012 ◽  
Vol 23 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
Yi Long ◽  
Zeng Li ◽  
Jia-Heng Tan ◽  
Tian-Miao Ou ◽  
Ding Li ◽  
...  
Keyword(s):  
Duplex Dna ◽  
Quadruplex Dna ◽  
Remarkable Improvement ◽  
G Quadruplex

Identification of a selective G-quadruplex DNA binder using a multistep virtual screening approach

2015 ◽  
Vol 51 (1) ◽  
pp. 198-201 ◽  
Author(s):  
Jin-Qiang Hou ◽  
Shuo-Bin Chen ◽  
Li-Peng Zan ◽  
Tian-Miao Ou ◽  
Jia-Heng Tan ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Duplex Dna ◽  
Quadruplex Dna ◽  
Screening Approach ◽  
G Quadruplex ◽  
Virtual Screening Approach

A selective G-quadruplex binder was identified using a multistep virtual screening approach by simultaneously taking into account G-quadruplex and duplex DNA.

scholarly journals Benzimidazole-1,2,3-triazole hybrid molecules: synthesis and study of their interaction with G-quadruplex DNA

2021 ◽  
Author(s):  
Padma S. Singu ◽  
Ushasri Chilakamarthi ◽  
Namita S. Mahadik ◽  
Bhamidipati Keerti ◽  
Narasimhulu Valipenta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Anticancer Activity ◽  
Duplex Dna ◽  
Quadruplex Dna ◽  
Hybrid Molecules ◽  
G Quadruplex ◽  
M Phase

The benzimidazole-1,2,3-triazole hybrid 4f selectively interacted with G-quadruplex DNA over duplex DNA, inhibits cell cycle at the G2/M phase, inducing apoptosis, and may be a G-quadruplex DNA groove binder with anticancer activity.

scholarly journals Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 733 ◽  
Author(s):  
Catarina Ramos ◽  
Susana Almeida ◽  
Leandro Lourenço ◽  
Patrícia Pereira ◽  
Rosa Fernandes ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Spectroscopic Techniques ◽  
Duplex Dna ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Telomerase Inhibitor ◽  
G Quadruplex ◽  
Bladder Cancer Cells ◽  
Selective Ligands ◽  
Inhibitor Selectivity

The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.

scholarly journals G-Quadruplex DNA Folding and Dynamics within Duplex DNA

2014 ◽  
Vol 106 (2) ◽  
pp. 64a
Author(s):  
Alex Kreig ◽  
Jacob Calvert ◽  
Ramreddy Tippana ◽  
Su-a Myong
Keyword(s):  
Duplex Dna ◽  
Quadruplex Dna ◽  
Dna Folding ◽  
G Quadruplex

scholarly journals Spectroscopic data for the G-quadruplex DNA to duplex DNA reaction

Data in Brief ◽  
2015 ◽  
Vol 5 ◽  
pp. 822-828
Author(s):  
Oscar Mendoza ◽  
Juan Elezgaray ◽  
Jean-Louis Mergny
Keyword(s):  
Spectroscopic Data ◽  
Duplex Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

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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