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Molecules 2018, 23(12), 3154; https://doi.org/10.3390/molecules23123154

Binding Study of the Fluorescent Carbazole Derivative with Human Telomeric G-Quadruplexes

1
Laboratory of Bioanalytical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland
2
Department of Clinical Chemistry and Molecular Diagnostics, University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznań, Poland
*
Author to whom correspondence should be addressed.
Received: 4 November 2018 / Revised: 28 November 2018 / Accepted: 29 November 2018 / Published: 30 November 2018
(This article belongs to the Special Issue G-Quadruplex Ligands and Cancer)
PDF [2467 KB, uploaded 30 November 2018]

Abstract

The carbazole ligand 3 was synthesized, characterized and its binding interactions with human telomeric (22HT) G-quadruplex DNA in Na+ and K+-containing buffer were investigated by ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence, circular dichroism (CD) spectroscopy, and DNA melting. The results showed that the studied carbazole ligand interacted and stabilized the intramolecular G-quadruplexes formed by the telomeric sequence in the presence of sodium and potassium ions. In the UV-Vis titration experiments a two-step complex formation between ligand and G-quadruplex was observed. Very low fluorescence intensity of the carbazole derivative in Tris HCl buffer in the presence of the NaCl or KCl increased significantly after addition of the 22HT G4 DNA. Binding stoichiometry of the ligand/G-quadruplex was investigated with absorbance-based Job plots. Carbazole ligand binds 22HT with about 2:1 stoichiometry in the presence of sodium and potassium ions. The binding mode appeared to be end-stacking with comparable binding constants of ~105 M−1 as determined from UV-Vis and fluorescence titrations data. The carbazole ligand is able to induce formation of G4 structure of 22HT in the absence of salt, which was proved by CD spectroscopy and melting studies. The derivative of carbazole 3 shows significantly higher cytotoxicity against breast cancer cells then for non-tumorigenic breast epithelial cells. The cytotoxic activity of ligand seems to be not associated with telomerase inhibition.
Keywords: G-quadruplex; telomere; carbazole derivative; biological activity; spectroscopy; telomerase G-quadruplex; telomere; carbazole derivative; biological activity; spectroscopy; telomerase
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Głuszyńska, A.; Juskowiak, B.; Rubiś, B. Binding Study of the Fluorescent Carbazole Derivative with Human Telomeric G-Quadruplexes. Molecules 2018, 23, 3154.

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