Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA
Timothy Kench, Viktoria Rakers, David Bouzada, Jacobo Gómez‐González, Jenna Robinson, Marina K. Kuimova, Miguel Vázquez López, M. Eugenio Vázquez, Ramón Vilar
Abstract
High Resolution Image Download MS PowerPoint Slide G-Quadruplex DNA structures have attracted increasing attention due to their biological roles and potential as targets for the development of new drugs. While most guanine-rich sequences in the genome have the potential to form monomeric G-quadruplexes, certain sequences have enough guanine-tracks to give rise to multimeric quadruplexes. One of these sequences is the human telomere where tandem repeats of TTAGGG can lead to the formation of two or more adjacent G-quadruplexes. Herein we report on the modular synthesis via click chemistry of dimeric metal-salphen complexes (with Ni II and Pt II ) bridged by either polyether or peptide linkers. We show by circular dichroism (CD) spectroscopy that they generally have higher selectivity for dimeric vs monomeric G-quadruplexes. The emissive properties of the Pt II -salphen dimeric complexes have been used to study their interactions with monomeric and dimeric G-quadruplexes in vitro as well as to study their cellular uptake and localization.