Citation
Abstract
Ruthenium(II) polypyridyl complexes (RPCs) that emit from metal-to-ligand charge transfer (MLCT) states have been developed as DNA probes and are being examined as potential anticancer agents. Here, we report that MLCT-emissive RPCs that bind DNA undergo Förster resonance energy transfer (FRET) with Cy5.5-labeled DNA, forming mega-Stokes shift FRET pairs. Based on this discovery, we developed a simple and rapid FRET binding assay to examine DNA-binding interactions of RPCs with diverse photophysical properties, including non-“light switch” complexes [Ru(dppz)2(5,5′dmb)]2+ and [Ru(PIP)2(5,5′dmb)]2+ (dppz = dipyridophenazine, 5,5′dmb = 5,5′-dimethyl-2,2′-bipyridine, PIP = 2-phenyl-imidazo[4,5-f][1,10]phenanthroline). Binding affinities toward duplex, G-quadruplex, three-way junction, and mismatch DNA were determined, and derived FRET donor–acceptor proximities provide information on potential binding sites. Molecules characterized by this method demonstrate encouraging anticancer properties, including synergy with the PARP inhibitor Olaparib, and mechanistic studies indicate that [Ru(PIP)2(5,5′dmb)]2+ acts to block DNA replication fork progression.
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Official URL or Download Paper: https://pubs.acs.org/doi/suppl/10.1021/jacs.2c1111...
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Additional Metadata
Item Type: | Article |
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Divisions: | Faculty of Science Institute of Bioscience |
DOI Number: | https://doi.org/10.1021/jacs.2c11111.s001 |
Publisher: | American Chemical Society (ACS) |
Keywords: | Metal-to-ligand charge transfer (MLCT); Ruthenium(II) polypyridyl complexes (RPCs); DNA binding; FRET binding assay; Anticancer properties |
Depositing User: | Ms. Nur Aina Ahmad Mustafa |
Date Deposited: | 10 Dec 2024 06:48 |
Last Modified: | 10 Dec 2024 06:48 |
Altmetrics: | http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1021/jacs.2c11111.s001 |
URI: | http://psasir.upm.edu.my/id/eprint/109445 |
Statistic Details: | View Download Statistic |
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