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Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality
In this paper, we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy and electrophoresis methods, on three oligonucleotide sequences, each containing one 3′-3′ and two 5′-5′ inversion of polarity sites, and four G-runs with a variable number of residues, name...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737522/ https://www.ncbi.nlm.nih.gov/pubmed/28666330 http://dx.doi.org/10.1093/nar/gkx566 |
Sumario: | In this paper, we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy and electrophoresis methods, on three oligonucleotide sequences, each containing one 3′-3′ and two 5′-5′ inversion of polarity sites, and four G-runs with a variable number of residues, namely two, three and four (mTG(2)T, mTG(3)T and mTG(4)T with sequence 3′-TG(n)T-5′-5′-TG(n)T-3′-3′-TG(n)T-5′-5′-TG(n)T-3′ in which n = 2, 3 and 4, respectively), in comparison with their canonical counterparts (TG(n)T)(4) (n = 2, 3 and 4). Oligonucleotides mTG(3)T and mTG(4)T have been proven to form very stable unprecedented monomolecular parallel G-quadruplex structures, characterized by three side loops containing the inversion of polarity sites. Both G-quadruplexes have shown an all-syn G-tetrad, while the other guanosines adopt anti glycosidic conformations. All oligonucleotides investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6 and colorectal cancer cell line HCT-116 (p53−/−). Interestingly, mTG(3)T and mTG(4)T have proven to be mostly resistant to nucleases in a fetal bovine serum assay. The whole of the data suggest the involvement of specific pathways and targets for the biological activity. |
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