scholarly journals Terpyridine–Cu(ii) targeting human telomeric DNA to produce highly stereospecific G-quadruplex DNA metalloenzyme

2015 ◽  
Vol 6 (10) ◽  
pp. 5578-5585 ◽  
Author(s):  
Yinghao Li ◽  
Mingpan Cheng ◽  
Jingya Hao ◽  
Changhao Wang ◽  
Guoqing Jia ◽  
...  
Keyword(s):  
Telomeric Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

A highly stereospecific G-quadruplex DNA metalloenzyme was found by exploring the G-quadruplex targeting ligand pool.

scholarly journals PhenQE8, a Novel Ligand of the Human Telomeric Quadruplex

2021 ◽  
Vol 22 (2) ◽  
pp. 749
Author(s):  
Patricia B. Gratal ◽  
Julia G. Quero ◽  
Adrián Pérez-Redondo ◽  
Zoila Gándara ◽  
Lourdes Gude
Keyword(s):  
Equilibrium Dialysis ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
The Novel ◽  
X Ray Diffraction ◽  
Telomeric Dna ◽  
Healthy Human ◽  
Quadruplex Dna ◽  
Step Procedure ◽  
G Quadruplex

A novel quadruplex ligand based on 1,10-phenanthroline and incorporating two guanyl hydrazone functionalities, PhenQE8, is reported herein. Synthetic access was gained in a two-step procedure with an overall yield of 61%. X-ray diffraction studies revealed that PhenQE8 can adopt an extended conformation that may be optimal to favor recognition of quadruplex DNA. DNA interactions with polymorphic G-quadruplex telomeric structures were studied by different techniques, such as Fluorescence resonance energy transfer (FRET) DNA melting assays, circular dichroism and equilibrium dialysis. Our results reveal that the novel ligand PhenQE8 can efficiently recognize the hybrid quadruplex structures of the human telomeric DNA, with high binding affinity and quadruplex/duplex selectivity. Moreover, the compound shows significant cytotoxic activity against a selected panel of cultured tumor cells (PC-3, HeLa and MCF-7), whereas its cytotoxicity is considerably lower in healthy human cells (HFF-1 and RPWE-1).

scholarly journals Pif1 helicase unfolding of G-quadruplex DNA is highly dependent on sequence and reaction conditions

2018 ◽  
Vol 293 (46) ◽  
pp. 17792-17802 ◽  
Author(s):  
Alicia K. Byrd ◽  
Matthew R. Bell ◽  
Kevin D. Raney
Keyword(s):  
Dna Sequences ◽  
Atp Hydrolysis ◽  
Monovalent Cation ◽  
Product Formation ◽  
Telomeric Dna ◽  
Reaction Conditions ◽  
Specific Sequence ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Pif1 Helicase

In addition to unwinding double-stranded nucleic acids, helicase activity can also unfold noncanonical structures such as G-quadruplexes. We previously characterized Pif1 helicase catalyzed unfolding of parallel G-quadruplex DNA. Here we characterized unfolding of the telomeric G-quadruplex, which can fold into antiparallel and mixed hybrid structures and found significant differences. Telomeric DNA sequences are unfolded more readily than the parallel quadruplex formed by the c-MYC promoter in K+. Furthermore, we found that under conditions in which the telomeric quadruplex is less stable, such as in Na+, Pif1 traps thermally melted quadruplexes in the absence of ATP, leading to the appearance of increased product formation under conditions in which the enzyme is preincubated with the substrate. Stable telomeric G-quadruplex structures were unfolded in a stepwise manner at a rate slower than that of duplex DNA unwinding; however, the slower dissociation from G-quadruplexes compared with duplexes allowed the helicase to traverse more nucleotides than on duplexes. Consistent with this, the rate of ATP hydrolysis on the telomeric quadruplex DNA was reduced relative to that on single-stranded DNA (ssDNA), but less quadruplex DNA was needed to saturate ATPase activity. Under single-cycle conditions, telomeric quadruplex was unfolded by Pif1, but for the c-MYC quadruplex, unfolding required multiple helicase molecules loaded onto the adjacent ssDNA. Our findings illustrate that Pif1-catalyzed unfolding of G-quadruplex DNA is highly dependent on the specific sequence and the conditions of the reaction, including both the monovalent cation and the order of addition.

scholarly journals Enantiomeric copper based anticancer agents promoting sequence-selective cleavage of G-quadruplex telomeric DNA and non-random cleavage of plasmid DNA

Metallomics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 988-999 ◽  
Author(s):  
Sabiha Parveen ◽  
J. A. Cowan ◽  
Zhen Yu ◽  
Farukh Arjmand
Keyword(s):  
Anticancer Agents ◽  
Plasmid Dna ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
Dna Cleaving ◽  
G Quadruplex

Copper-based enantiomeric anticancer agents (1S and 1R) were synthesized and studied as sequence-selective G-quadruplex DNA cleaving agents.

Interactions of selected gold(iii) complexes with DNA G quadruplexes

2015 ◽  
Vol 44 (8) ◽  
pp. 3633-3639 ◽  
Author(s):  
P. Gratteri ◽  
L. Massai ◽  
E. Michelucci ◽  
R. Rigo ◽  
L. Messori ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Dna Conformation ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

The interactions of three Au(iii) complexes with human telomeric DNA sequences: Auoxo6 turned out to be very effective in inducing and binding the G-quadruplex DNA conformation.

Some cationic porphyrins: synthesis, stabilization of G-quadruplexes, and down-regulation of c-myc in Hep G2 cells

2009 ◽  
Vol 13 (08n09) ◽  
pp. 865-875 ◽  
Author(s):  
Shao R. Wang ◽  
Dan Zhang ◽  
Feng L. Luo ◽  
Lin Liu ◽  
Xiao C. Weng ◽  
...  
Keyword(s):  
Cell Line ◽  
Binding Assays ◽  
Hep G2 ◽  
Hep G2 Cells ◽  
Telomeric Dna ◽  
Down Regulation ◽  
Cationic Porphyrins ◽  
Quadruplex Dna ◽  
Myc Oncogene ◽  
G Quadruplex

The stabilization of G-quadruplex DNA represents an attractive strategy for the design and development of novel antitumor drugs. In the present work, we have designed and synthesized nine cationic porphyrins, each with four side arms at their meso positions. The interactions of these porphyrins with both human telomeric DNA and NHE III1 G-quadruplexes were measured by various DNA binding assays, including polymerase stop assay, circular dichroism (CD) and CD melting assay. We then proceeded to investigate their effects on the expression of c-myc oncogene in the Hep G2 cell line. The experimental results indicate that these porphyrins are capable of effectively inducing or stabilizing both human telomeric and NHE III1 G-quadruplexes in the presence or absence of metal ions. Furthermore, we have discovered that porphyrins with a stronger stabilizing effect on c-myc G-quadruplexes lead to more pronounced down-regulation of the c-myc oncogene in the Hep G2 cell line.

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.

G-Quadruplex DNA-binding quaternary alkaloids from Tylophora atrofolliculata

RSC Advances ◽  
2016 ◽  
Vol 6 (115) ◽  
pp. 114135-114142 ◽  
Author(s):  
Cheng-Yu Chen ◽  
Li-Ping Bai ◽  
Zhuo-Feng Ke ◽  
Yan Liu ◽  
Jing-Rong Wang ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Capacity ◽  
Telomeric Dna ◽  
Quadruplex Dna ◽  
G Quadruplex

Quaternary alkaloids from T. atrofolliculata with human telomeric DNA G-quadruplex binding capacity.

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
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