Monomolecular G-quadruplex structures with inversion of polarity sites: new topologies and potentiality.
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| Abstract |
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 (mTG2T, mTG3T and mTG4T with sequence 3'-TGnT-5'-5'-TGnT-3'-3'-TGnT-5'-5'-TGnT-3' in which n = 2, 3 and 4, respectively), in comparison with their canonical counterparts (TGnT)4 (n = 2, 3 and 4). Oligonucleotides mTG3T and mTG4T 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, mTG3T and mTG4T 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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| Authors | Antonella Virgilio, Annapina Russo, Teresa Amato, Giulia Russo, Luciano Mayol, Veronica Esposito, Aldo Galeone |
| Journal | Nucleic acids research (Nucleic Acids Res) Vol. 45 Issue 14 Pg. 8156-8166 (Aug 21 2017) ISSN: 1362-4962 [Electronic] England |
| PMID | 28666330 (Publication Type: Journal Article) |
| Copyright | © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. |
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