Ruthenation of Non‐stacked Guanines in DNA G‐Quadruplex Structures: Enhancement of c‐MYC Expression

Guanine quadruplexes (GQs) are compact four‐stranded DNA structures that play a key role in the control of a variety of biological processes, including gene transcription. Bulky ruthenium complexes featuring a bipyridine, a terpyridine, and one exchangeable ligand ([Ru(terpy)(bpy)X]n+) are able to metalate exposed guanines present in the GQ of the c‐MYC promoter region that are not involved in quadruplex base pairing. qRT‐PCR and western‐blot experiments indicated that the complexes promote a remarkable increase in the expression of this oncogene. We also show that exchangeable thioether ligands (X=RSR′, Met) allow regulation of the metalating activity of the complex with visible lightWe thank the support by the Spanish grants SAF2013‐41943‐R, CTQ2015‐70698‐R, and CTQ2013‐49317‐EXP, the Xunta de Galicia GRC2013‐041, the ERDF, and the European Research Council (Advanced Grant No. 340055). Support of COST Action CM1105, COST CM1306 and the orfeo‐cinqa network are also kindly acknowledged. J.R. thanks the Xunta de Galicia for a Ph.D. fellowshipS