Fersiynau electronig


Dangosydd eitem ddigidol (DOI)

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) (5,5'dmb)] and [Ru(PIP) (5,5'dmb)] (dppz = dipyridophenazine, 5,5'dmb = 5,5'-dimethyl-2,2'-bipyridine, PIP = 2-phenyl-imidazo[4,5- ][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) (5,5'dmb)] acts to block DNA replication fork progression.


Iaith wreiddiolSaesneg
Tudalennau (o-i)1236-1246
Nifer y tudalennau11
CyfnodolynJournal of the American Chemical Society
Rhif y cyfnodolyn2
Dyddiad ar-lein cynnar6 Ion 2023
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 18 Ion 2023

Cyfanswm lawlrlwytho

Nid oes data ar gael
Gweld graff cysylltiadau