Contents lists available at ScienceDirect Journal of Electroanalytical Chemistry journal homepage: www.elsevier.com/locate/jelechem A new electrochemical biosensor based on telomeric G-quadruplex DNA: In silico and experimental study of dihydropyridine derivatives potential effect on telomerase inhibition Roghayyeh Aghaei a , Mohammad Mazloum-Ardakani a,⁎ , Mohammad Abdollahi-Alibeik a , Seyed Mohammad Moshtaghioun b , Ali Rezaeipoor-Anari a , Zahra Haghighijoo c,d , Leila Zamani e a Department of Chemistry, Faculty of Science, Yazd University, Yazd, Yazd 89195-741, Iran b Department of Biology, Faculty of Science, Yazd University, Yazd 89195-741, Iran c Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran d Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran e Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ARTICLE INFO Keywords: Telomeric G-Quadruplex DNA In silico Au nanoparticles Electrochemical biosensor Dihydropyridine ABSTRACT The electrochemical biosensor was prepared by modification of a glassy carbon electrode (GCE) with Au nanoparticles (AuNPs), G-quadruplex DNA (G 4 DNA) and i-motif DNA (C 4 DNA or i-DNA) structures to investigate of telomerase enzyme inhibitors. SH-G 4 DNA and SH-i-DNA were linked to the modified electrode by AuNPs–S binding. This platform was used to study the quadruplex DNA/ligand interaction. The interaction of different ligands with quadruplex DNA was studied in a 5.0 mM [Fe(CN) 6 ] 3 −/4 − solution as a redox probe at the surface of these biosensors, using the electrochemical impedance spectroscopy (EIS) technique. The resistance of charge transfer (R ct ) values was increased by increasing the concentration of ligand due to the quadruplex DNA/ligand interaction. Under the optimum conditions, the observations revealed that 1,4-dihydropyridine (1,4-DHP) derivatives had a good affinity toward the quadruplex DNA structures in the concentration range of 5.0–700.0 μM. The selectivity was examined using different double-stranded (ds-DNA) sequences. 1. Introduction Telomeric DNA, while it is associated with the Shelterin nucleopro- tein complex, can protect chromosomal ends from end-to-end fusions and consequently DNA damage and also the mentioned complex with the enzyme telomerase plays a pivotal role in telomere length regula- tion [1,2]. The telomerase actively extends the length of telomeric DNA by addition of d(TTAGGG) repeats to the 3′ terminus to ensure chromosomal integrity after each cell cycle. Under physiological concentrations of Na + and K + , in vitro, guanine-rich DNA sequences can fold into stable four-stranded G-quadruplex structures. While motifs sequence folds into quadruplexes under the control of specific telomere binding proteins, they can be found in the telomeres [3,4]. G- quadruplex motifs have been identified throughout the genome and concentrate immediately upstream of transcription initiation sites [5]. The self-complementary nature of duplex DNA can cause the presence of approximately 370′000 C-rich motifs (C 3+ N 1–7 ) 4+ (where C = cytosine and N = any base) in the human genome [6–8]. The mentioned C-rich sequences can fold into a type of tetraplex called ‘i- motif’ that contains hemi-protonated, intercalated C–C + base pairs, under slightly acidic conditions (pH = 6). For the best of our knowl- edge, almost nothing is known about the presence or biological relevance of i-motif DNA in vivo [7]. Thus, these results indicate that i-motifs might be formed under physiological conditions in vivo through molecular binding and/or crowding interactions [9]. As known, telomerase is up-regulated in 85% of human cancers, with minimal activity in somatic cells, making telomerase as an attractive target for therapeutic intervention in cancer. A number of methods have been developed for telomerase inhibition [10–13]. Up to now, many small molecules that bind to telomeric quadruplexes have been developed but none of them have been fully used as an anticancer therapeutics, due to low potency and selectivity. Unfortunately, in vivo antitumor data is mostly restricted to acridine-derived compounds and the natural product telomestatin. So, selection of a ligand with a good affinity toward G-quadruplex to stabilize or fold its structure is a good suggestion for cancer therapy. The designed ligands with high affinity with G-quadruplex could inhibit the telomerase activity, which is important in the treatment of cancers [14–19]. Choosing a ligand with http://dx.doi.org/10.1016/j.jelechem.2017.04.055 Received 6 February 2017; Received in revised form 26 April 2017; Accepted 28 April 2017 ⁎ Corresponding author. E-mail address: mazloum@yazd.ac.ir (M. Mazloum-Ardakani). Journal of Electroanalytical Chemistry 796 (2017) 24–32 Available online 02 May 2017 1572-6657/ © 2017 Elsevier B.V. All rights reserved. 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