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Development of polyamine substituted triphenylamine ligands with high affinity and selectivity for G-quadruplex DNA

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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