Aza-Macrocyclic Triphenylamine Ligands for G-Quadruplex Recognition

Isabel Pont; Jorge González-García; Mario Inclán; Matthew Reynolds; Estefanía Delgado-Pinar; M Teresa Albelda; Ramon Vilar; Enrique García-España

doi:10.1002/chem.201802077

Aza-Macrocyclic Triphenylamine Ligands for G-Quadruplex Recognition

Chemistry. 2018 Jul 25;24(42):10850-10858. doi: 10.1002/chem.201802077. Epub 2018 Jun 27.

Authors

Isabel Pont^{1

2}, Jorge González-García^{1

2}, Mario Inclán¹, Matthew Reynolds², Estefanía Delgado-Pinar¹, M Teresa Albelda^{1

3}, Ramon Vilar², Enrique García-España¹

Affiliations

¹ Department of Inorganic Chemistry, Institute of Molecular Science, University of Valencia, Catedrático José Beltran 2, 46980, Paterna, Spain.
² Department of Chemistry, Imperial College London, London, SW7 2AZ, UK.
³ GIBI2030, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia, Spain.

PMID: 29768679
DOI: 10.1002/chem.201802077

Abstract

A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pendant aza-macrocycle(s) (TPA3PY) has been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and the selectivity they show for G4s over duplex DNA were investigated by Förster resonance energy transfer (FRET) melting assays, fluorimetric titrations and circular dichroism spectroscopy. Interestingly, the interactions of the bi- and especially the tri-branched ligands with G4s lead to a very intense redshifted fluorescence emission band that may be associated with intermolecular aggregation between the molecule and DNA. This light-up effect allows the application of the ligands as fluorescence probes to selectively detect G4s.

Keywords: DNA; G-quadruplexes; aggregation; amines; fluorescent probes; macrocyclic ligands.