Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA

靶向多聚体 G-四链体 DNA 的二聚体金属-Salphen 复合物

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作者:Timothy Kench, Viktoria Rakers, David Bouzada, Jacobo Gomez-González, Jenna Robinson, Marina K Kuimova, Miguel Vázquez López, M Eugenio Vázquez, Ramon Vilar

Abstract

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 NiII and PtII) 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 PtII-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.

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