Virgilio Antonella, Russo Annapina, Amato Teresa, Russo Giulia, Mayol Luciano, Esposito Veronica, Galeone Aldo
Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy.
Nucleic Acids Res. 2017 Aug 21;45(14):8156-8166. doi: 10.1093/nar/gkx566.
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.
在本文中，我们报告了基于圆二色性、核磁共振光谱和电泳方法，对三个寡核苷酸序列的研究。每个序列都包含一个3'-3'和两个5'-5'极性反转位点，以及四个具有不同残基数目的G-链，即两个、三个和四个（分别为mTG2T、mTG3T和mTG4T，序列为3'-TGnT-5'-5'-TGnT-3'-3'-TGnT-5'-5'-TGnT-3'，其中n = 2、3和4），并与它们的经典对应物(TGnT)4（n = 2、3和4）进行比较。已证明寡核苷酸mTG3T和mTG4T能形成非常稳定的前所未有的单分子平行G-四链体结构，其特征是有三个包含极性反转位点的侧环。两个G-四链体均显示出全顺式G-四联体，而其他鸟苷则采用反式糖苷构象。所有研究的寡核苷酸均对肺癌细胞系Calu 6和结肠癌细胞系HCT-116 p53-/-表现出显著的抗增殖活性。有趣的是，在胎牛血清试验中，mTG3T和mTG4T已被证明对核酸酶大多具有抗性。所有数据表明特定途径和靶点参与了生物活性。
