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

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 t...

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Bibliographic Details
Published in:Bioconjugate chemistry 2023-05, Vol.34 (5), p.911-921
Main Authors: Kench, Timothy, Rakers, Viktoria, Bouzada, David, Gomez-González, Jacobo, Robinson, Jenna, Kuimova, Marina K., Vázquez López, Miguel, Vázquez, M. Eugenio, Vilar, Ramon
Format: Article
Language:English
Subjects:
Chemical synthesis
Circular Dichroism
Coordination Complexes - chemistry
Deoxyribonucleic acid
Dichroism
Dimers
DNA
DNA - chemistry
Drug development
G-Quadruplexes
Gene sequencing
Genomes
Guanine - chemistry
Humans
Localization
Nucleotide sequence
Polymers
Spectroscopy
Telomere
Telomeres
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Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.3c00114