Asymmetric triplex metallohelices stabilise DNA G-quadruplexes in promoter oncogene sequences and efficiently reduce their expression in cancer cells
Autor: | Jaroslav Malina, Hana Kostrhunova, Hualong Song, Peter Scott, Viktor Brabec |
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Jazyk: | angličtina |
Rok vydání: | 2023 |
Předmět: | |
Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 38, Iss 1 (2023) |
Druh dokumentu: | article |
ISSN: | 14756366 1475-6374 1475-6366 |
DOI: | 10.1080/14756366.2023.2198678 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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