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Development of polyamine substituted triphenylamine ligands with high affinity and selectivity for G-quadruplex DNA
File | Description | Size | Format | |
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Accepted-Manuscript.pdf | Accepted version | 1.3 MB | Adobe PDF | View/Open |
Accepted-ESI.pdf | Supporting information | 3.12 MB | Adobe PDF | View/Open |
Title: | Development of polyamine substituted triphenylamine ligands with high affinity and selectivity for G-quadruplex DNA |
Authors: | Pont, I Martínez-Camarena, Á Galiana-Roselló, C Tejero, R Albelda, MT González-García, J Vilar, R García-España, EV |
Item Type: | Journal Article |
Abstract: | Currently significant efforts are devoted to designing small molecules able to bind selectively to guanine-quadruplexes (G4s). These non-canonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, we reported a series of triphenylamine(TPA)-based compounds including macrocyclic polyamines, which display high affinity towards G4 DNA. Following from this initial work, herein we present a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, aiming to maximise the selectivity towards G4 DNA. The acid-base properties of the new derivatives have been studied by means of potentiometric titrations, UV-Vis and fluorescence emission spectroscopies. The interaction with G4s and duplex DNA has been explored using FRET melting assays, fluorescence spectroscopy and circular dichroism. Compared to our previously TPA derivatives with macrocyclic substituents, the new ligands reported herein retain the G4 affinity, but display two orders of magnitude higher selectivity for G4 vs. duplex DNA, most likely due to the ability of the linear substituents to embrace the G4 structure. |
Issue Date: | 17-Apr-2020 |
Date of Acceptance: | 7-Nov-2019 |
URI: | http://hdl.handle.net/10044/1/75639 |
DOI: | 10.1002/cbic.201900678 |
ISSN: | 1439-4227 |
Publisher: | Wiley |
Start Page: | 1167 |
End Page: | 1177 |
Journal / Book Title: | ChemBioChem: a European journal of chemical biology |
Volume: | 21 |
Issue: | 8 |
Copyright Statement: | © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/abs/10.1002/cbic.201900678. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Chemistry, Medicinal Pharmacology & Pharmacy DNA fluorescence FRET G-quadruplexes polyamines COORDINATION CHEMISTRY EQUILIBRIUM-CONSTANTS COMPLEXES EMISSION PROBE DNA FRET G-quadruplexes fluorescence polyamines * G-quadruplex DNA * G4 selectivity * polyamine-based ligand *fluorescence 0304 Medicinal and Biomolecular Chemistry 0601 Biochemistry and Cell Biology Organic Chemistry |
Publication Status: | Published |
Conference Place: | Germany |
Online Publication Date: | 2019-11-08 |
Appears in Collections: | Chemistry Biological and Biophysical Chemistry Faculty of Natural Sciences |