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Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
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Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
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Journal Article
Multicharged Phthalocyanines as Selective Ligands for G-Quadruplex DNA Structures
2019
Overview
The stabilization of G-Quadruplex DNA structures by ligands is a promising strategy for telomerase inhibition in cancer therapy since this enzyme is responsible for the unlimited proliferation of cancer cells. To assess the potential of a compound as a telomerase inhibitor, selectivity for quadruplex over duplex DNA is a fundamental attribute, as the drug must be able to recognize quadruplex DNA in the presence of a large amount of duplex DNA, in the cellular nucleus. By using different spectroscopic techniques, such as ultraviolet-visible, fluorescence and circular dichroism, this work evaluates the potential of a series of multicharged phthalocyanines, bearing four or eight positive charges, as G-Quadruplex stabilizing ligands. This work led us to conclude that the existence of a balance between the number and position of the positive charges in the phthalocyanine structure is a fundamental attribute for its selectivity for G-Quadruplex structures over duplex DNA structures. Two of the studied phthalocyanines, one with four peripheral positive charges (ZnPc1) and the other with less exposed eight positive charges (ZnPc4) showed high selectivity and affinity for G-Quadruplex over duplex DNA structures and were able to accumulate in the nucleus of UM-UC-3 bladder cancer cells.
Publisher
MDPI AG,MDPI
Subject
/ Cancer
/ Coordination Complexes - chemistry
/ DNA
/ Enzyme Inhibitors - chemistry
/ Enzymes
/ Fluorescent Dyes - chemistry
/ G-Quadruplexes - drug effects
/ G4-FID
/ Humans
/ Ligands
/ multicharged phthalocyanines
/ Spectrometry, Fluorescence - methods
/ Sperm
/ Structure-Activity Relationship
/ Telomerase - antagonists & inhibitors
/ UV-Vis
