A new electrochemical biosensor based on telomeric G-quadruplex DNA: In silico and experimental study of dihydropyridine derivatives potential effect on telomerase inhibition

Aghaei, Roghayyeh; Mazloum-Ardakani, Mohammad; Abdollahi‐Alibeik, Mohammad; Moshtaghioun, Seyed Mohammad; Rezaeipoor-Anari, Ali; Haghighijoo, Zahra; Zamani, Leila

doi:10.1016/j.jelechem.2017.04.055

Cited by 12 publications

(7 citation statements)

References 42 publications

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“…1,4-DHP derivatives can also bind unusual DNA structure -the G-quadruplexes, that we demonstrated for the AV-153 salts, with Na and K effectively binding the human telomere repeat in G4 form [17]. Binding to guanine quadruplexes was also shown for a series of novel derivatives [22].…”

Section: In Vitro Molecular Interactions and Dna Bindingsupporting

confidence: 57%

Genome protecting and genotoxic effects produced by derivatives of 1,4-dihydropyridine

Ļeonova

Ryabokon

Rostoka

et al. 2022

Preprint

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The review summarizes data on genome protecting and genotoxic action of 1,4-dihydropyridines (DHP) with main focus on the compounds synthesized in the Latvian Institute of Organic synthesis. Most of these compounds manifest very low calcium channel blocking activity, thus considered to be “unusual” 1,4-DHP. Some of these compounds decrease spontaneous mutagenesis and frequency of mutations induced by chemical mutagens. Some water-soluble 1,4-DHP protect DNA against damage produced by hydrogen peroxide, radiation and peroxynitrite. In these molecules capability to protect DNA cohabitates with DNA-binding activity. Possible mechanisms of above effects are discussed.

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Section: In Vitro Molecular Interactions and Dna Bindingsupporting

confidence: 57%

Genome protecting and genotoxic effects produced by derivatives of 1,4-dihydropyridine

Ļeonova

Ryabokon

Rostoka

et al. 2022

Preprint

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“…The possible interaction mechanism was evaluated by means of EtBr displacement assay, circular dichroism, and infrared spectroscopy. We also tested the affinity of the AV-153 salts to telomeric repeats after taking the great interest in G-quadruplex-targeting drugs and recent reports on the possible application of the 1,4-DHP as G-quadruplex sensors into account (Aghaei et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153

Ļeonova

Shvirksts

Borisovs

et al. 2020

PeerJ

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1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antimutagenic and DNA-binding activity. The latter activity was first described for water-soluble 1,4-DHP with carboxylic group in position 4, the sodium salt of the 1,4-DHP derivative AV-153 among others. Some data show the modification of physicochemical properties and biological activities of organic compounds by metal ions that form the salts. We demonstrated the different affinity to DNA and DNA-protecting capacity of AV-153 salts, depending on the salt-forming ion (Na, K, Li, Rb, Ca, Mg). This study aimed to use different approaches to collate data on the DNA-binding mode of AV-153-Na and five other AV-153 salts. All the AV-153 salts in this study quenched the ethidium bromide and DNA complex fluorescence, which points to an intercalation binding mode. For some of them, the intercalation binding was confirmed using cyclic voltammetry and circular dichroism spectroscopy. It was shown that in vitro all AV-153 salts can interact with four DNA bases. The FTIR spectroscopy data showed the interaction of AV-153 salts with both DNA bases and phosphate groups. A preference for base interaction was observed as the AV-153 salts interacted mostly with G and C bases. However, the highest differences were detected in the spectral region assigned to phosphate groups, which might indicate either conformational changes of DNA molecule (B form to A or H form) or partial denaturation of the molecule. According to the UV/VIS spectroscopy data, the salts also interact with the human telomere repeat, both in guanine quadruplex (G4) and single-stranded form; Na and K salts manifested higher affinity to G4, Li and Rb –to single-stranded DNA.

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“…Several strategies based on the telomeric repeat amplification protocol (TRAP) , have been developed for detecting telomerase activity, such as the electrochemical method, − surface-enhanced Raman scattering, , and fluorescent method. − These methods have significantly improved the sensitivity and feasibility of telomerase activity detection, but they still suffer from several drawbacks that include being time-consuming and requiring expensive instruments and sophisticated experimental steps. In contrast, the fluorescent method holds great promise for telomerase activity detection because of its high signal intensity, real-time detection, and easy use and visualization.…”

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confidence: 99%

Ratiometric Fluorescent Biosensor for Visual Discrimination of Cancer Cells with Different Telomerase Expression Levels

Liu

et al. 2018

ACS Sens.

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Telomerase is inactive in normal somatic cells but highly activated in tumor cells to maintain their indefinite proliferation and immortal phenotype. As a specific marker for the generation and progress of almost all tumors, the detection of telomerase activity by classical PCR techniques has served in the biological research of tumors. However, the detection of in situ telomerase activity in cell extracts to evaluate the malignancy, progress, and metastasis of tumors remains a daunting challenge. Here, a precisely designed FRET-based ratiometric fluorescent oligonucleotide probe has achieved high-fidelity detection of telomerase activity for accurate discrimination of different cancer cells toward advanced diagnosis of tumors. Our method is superior to other methods in its capabilities to quantify telomerase activity in cell extracts and visualize various tumor cell extracts with different telomerase expression levels by the naked eye for clinical diagnosis. In particular, the ratiometric fluorescent probe used in the assay could exclude other experimental factors influence, and further avoid false positive signal generation. The method reported here could provide a reliable, accurate, and convenient way in medical diagnostics and therapeutic response assessment.

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A new electrochemical biosensor based on telomeric G-quadruplex DNA: In silico and experimental study of dihydropyridine derivatives potential effect on telomerase inhibition

Cited by 12 publications

References 42 publications

Genome protecting and genotoxic effects produced by derivatives of 1,4-dihydropyridine

Genome protecting and genotoxic effects produced by derivatives of 1,4-dihydropyridine

Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153

Ratiometric Fluorescent Biosensor for Visual Discrimination of Cancer Cells with Different Telomerase Expression Levels

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