Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties
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...
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| Format: | Article |
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American Chemical Society (ACS)
2023
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| author | E. Elgar, Christopher Yusoh, Nur Aininie R. Tiley, Paul Kolozsvári, Natália G. Bennett, Laura Gamble, Amelia V. Péan, Emmanuel L. Davies, Matthew J. Staples, Christopher Ahmad, Haslina R. Gill, Martin |
| author_facet | E. Elgar, Christopher Yusoh, Nur Aininie R. Tiley, Paul Kolozsvári, Natália G. Bennett, Laura Gamble, Amelia V. Péan, Emmanuel L. Davies, Matthew J. Staples, Christopher Ahmad, Haslina R. Gill, Martin |
| author_sort | E. Elgar, Christopher |
| collection | UPM |
| description | 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. |
| first_indexed | 2025-02-19T02:47:16Z |
| format | Article |
| id | upm.eprints-109445 |
| institution | Universiti Putra Malaysia |
| last_indexed | 2025-02-19T02:47:16Z |
| publishDate | 2023 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | upm.eprints-1094452024-12-10T06:48:27Z http://psasir.upm.edu.my/id/eprint/109445/ Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties E. Elgar, Christopher Yusoh, Nur Aininie R. Tiley, Paul Kolozsvári, Natália G. Bennett, Laura Gamble, Amelia V. Péan, Emmanuel L. Davies, Matthew J. Staples, Christopher Ahmad, Haslina R. Gill, Martin 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. American Chemical Society (ACS) 2023-01-06 Article PeerReviewed E. Elgar, Christopher and Yusoh, Nur Aininie and R. Tiley, Paul and Kolozsvári, Natália and G. Bennett, Laura and Gamble, Amelia and V. Péan, Emmanuel and L. Davies, Matthew and J. Staples, Christopher and Ahmad, Haslina and R. Gill, Martin (2023) Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties. Journal of the American Chemical Society, 145 (2). pp. 1236-1246. ISSN 0002-7863 https://pubs.acs.org/doi/suppl/10.1021/jacs.2c11111/suppl_file/ja2c11111_si_001.pdf 10.1021/jacs.2c11111.s001 |
| spellingShingle | E. Elgar, Christopher Yusoh, Nur Aininie R. Tiley, Paul Kolozsvári, Natália G. Bennett, Laura Gamble, Amelia V. Péan, Emmanuel L. Davies, Matthew J. Staples, Christopher Ahmad, Haslina R. Gill, Martin Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title | Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title_full | Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title_fullStr | Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title_full_unstemmed | Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title_short | Ruthenium(ii) Polypyridyl complexes as FRET donors: structure- and sequence-selective DNA binding and anti-cancer properties |
| title_sort | ruthenium ii polypyridyl complexes as fret donors structure and sequence selective dna binding and anti cancer properties |
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