Alkylating probes for the G-quadruplex structure and evaluation of the properties of the alkylated G-quadruplex DNA

2018 ◽  
Vol 16 (9) ◽  
pp. 1436-1441 ◽  
Author(s):  
Norihiro Sato ◽  
Shuntaro Takahashi ◽  
Hisae Tateishi-Karimata ◽  
Madoka E. Hazemi ◽  
Tomoko Chikuni ◽  
...  
Keyword(s):  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex

In this paper, we report the development of a new G-4 alkylating molecule and the evaluation of the properties of the alkylated G-4 DNA.

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 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.

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.

Selective alkylation of parallel G-quadruplex structure

2021 ◽  
Vol 19 (13) ◽  
pp. 2891-2894
Author(s):  
Kazumitsu Onizuka ◽  
Erchissaran Ganbold ◽  
Yue Ma ◽  
Shogo Sasaki ◽  
Madoka E. Hazemi ◽  
...  
Keyword(s):  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Selective Alkylation

We achieve selective alkylation of parallel G-quadruplex DNA using a conjugate of a macrocyclic hexaoxazole and a sulfoxide precursor to a vinyl-quinazolinone.

Anticancer Activity of Platinum (II) Complex as G-Quadruplex DNA Binders

2013 ◽  
Vol 781-784 ◽  
pp. 1130-1133
Author(s):  
Qi Pin Qin ◽  
Yu Lan Li ◽  
Yan Cheng Liu ◽  
Xu Jian Luo
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Normal Cell ◽  
Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Dna Binders

A platinum (II) complex has been synthesized and characterized. The complex binding properties with G-quadruplex DNA and ds26 were examined by FID and CD spectroscopic methods. The results revealed that the platinum (II) complex can induce the antiparallel G-quadruplex structure of HTG21 conformation in the absence of added K+ with selectivity over other G-quadruplex DNA and duplex DNA. The cytotoxicity of the platinum (II) was screened against four cancer cell lines and normal cells of HL-7702 in comparison to cisplatin and it showed a higher activity than cisplatin, with inhibition rates ranging from (40.06±1.65)% to (89.47±1.14)%. Furthermore, the platinum (II) complex displayed lower cytotoxic activities to HL-7702 (normal cell) compared with the cancer cell lines.

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.

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