Natalia Bartyś, Anna Pasternak, Jolanta Lisowiec-Wąchnicka
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Modified Nucleotides in Bifunctional Antisense Oligonucleotides: Exploring their Anticancer Potential
Bifunctional antisense oligonucleotides (BASOs) are splice-switching molecular tools composed of two, functional parts, that is, antisense part that hybridizes to target pre-messenger RNA fragment and regulatory part that recruits splicing factors to that localization. The aim is to verify the influence of variously modified nucleotides on alternative splicing regulation of the pyruvate kinase M1/2 gene and the anticancer potential of BASOs. The effect of modified BASOs on the phenotype of cancer cells is evaluated by real-time measurement of cell proliferation and motility. The studies reveal chemical modifications that significantly increase the therapeutic properties of BASOs as evidenced by decrease in cell proliferation rate, cancer cell death, and reduced motility. As the most promising modifications, it is considered that β-L-RNA and unlocked nucleic acid, present in BASOs, not only show splicing regulatory properties but also anticancer effects. The studies propose efficient modifications that might be used in protein-binding oligonucleotides to improve their therapeutic efficacy.
期刊介绍:
Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
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