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Asymmetric triplex metallohelices stabilise DNA G-quadruplexes in promoter oncogene sequences and efficiently reduce their expression in cancer cells
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Malina, Jaroslav, Kostrhunova, Hana, Song, Hualong, Scott, Peter and Brabec, Viktor (2023) Asymmetric triplex metallohelices stabilise DNA G-quadruplexes in promoter oncogene sequences and efficiently reduce their expression in cancer cells. Journal of Enzyme Inhibition and Medicinal Chemistry, 38 (1). 2198678. doi:10.1080/14756366.2023.2198678 ISSN 1475-6366.
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WRAP-asymmetric-triplex-metallohelices-stabilise-DNA-G-quadruplexes-promoter-oncogene-sequences-efficiently-reduce-expression-cancer-cells-2023.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2125Kb) | Preview |
Official URL: https://doi.org/10.1080/14756366.2023.2198678
Abstract
Some metallo-supramolecular helical assemblies with size, shape, charge and amphipathic architectures similar to short cationic α-helical peptides have been shown to target and stabilise DNA G-quadruplexes (G4s) in vitro and downregulate the expression of G4-regulated genes in human cells. To expand the library of metallohelical structures that can act as efficient DNA G4 binders and downregulate genes containing G4-forming sequences in their promoter regions, we investigated the interaction of the two enantiomeric pairs of asymmetric Fe(II) triplex metallohelices with a series of five different DNA G4s formed by the human telomeric sequence (hTelo) and in the promoter regions of c-MYC, c-KIT, and k-RAS oncogenes. The metallohelices display preferential binding to G4s over duplex DNA in all investigated G4-forming sequences and induced arrest of DNA polymerase on template strands containing G4-forming sequences. Moreover, the investigated metallohelices suppressed the expression of c-MYC and k-RAS genes at mRNA and protein levels in HCT116 human cancer cells, as revealed by RT-qPCR analysis and western blotting.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
Library of Congress Subject Headings (LCSH): | Organometallic compounds, Quadruplex nucleic acids, Supramolecular chemistry, Cancer cells | ||||||||
Journal or Publication Title: | Journal of Enzyme Inhibition and Medicinal Chemistry | ||||||||
Publisher: | Taylor and Francis Group | ||||||||
ISSN: | 1475-6366 | ||||||||
Official Date: | 2023 | ||||||||
Dates: |
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Volume: | 38 | ||||||||
Number: | 1 | ||||||||
Article Number: | 2198678 | ||||||||
DOI: | 10.1080/14756366.2023.2198678 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 13 April 2023 | ||||||||
Date of first compliant Open Access: | 13 April 2023 | ||||||||
RIOXX Funder/Project Grant: |
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