| Autor: |
Elgar CE; Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea SA2 8PP, U.K., Yusoh NA; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia., Tiley PR; Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea SA2 8PP, U.K., Kolozsvári N; Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea SA2 8PP, U.K., Bennett LG; North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor LL57 2DG, U.K., Gamble A; North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor LL57 2DG, U.K., Péan EV; SPECIFIC IKC, Materials Science and Engineering, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, U.K., Davies ML; SPECIFIC IKC, Materials Science and Engineering, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, U.K., Staples CJ; North West Cancer Research Institute, School of Medical Sciences, Bangor University, Bangor LL57 2DG, U.K., Ahmad H; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia., Gill MR; Department of Chemistry, Faculty of Science and Engineering, Swansea University, Swansea SA2 8PP, U.K. |
| Abstrakt: |
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. |
