Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, I-80131 Naples, Italy.
Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, I-80131 Naples, Italy.
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt B):1213-1221. doi: 10.1016/j.bbagen.2016.09.019. Epub 2016 Sep 20.
The thrombin binding aptamer (TBA) is endowed with antiproliferative properties but its potential development is counteracted by the concomitant anticoagulant activity.
Five oligonucleotides (ODNs) based on TBA sequence (GGTTGGTGTGGTTGG) and containing l-residues or both l-residues and inversion of polarity sites have been investigated by NMR and CD techniques for their ability to form G-quadruplex structures. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay), and their resistance in fetal bovine serum have been tested.
CD and NMR data suggest that the investigated ODNs are able to form right- and left-handed G-quadruplex structures. All ODNs do not retain the anticoagulant activity characteristic of TBA but are endowed with a significant antiproliferative activity against two cancerous cell lines. Their resistance in biological environment after six days is variable, depending on the ODN.
A comparison between results and literature data suggests that the antiproliferative activity of the TBA analogues investigated could depends on two factors: a) biological pathways and targets different from those already identified or proposed for other antiproliferative G-quadruplex aptamers, and b) the contribution of the guanine-based degradation products.
Modified TBA analogues containing l-residues and inversion of polarity sites lose the anticoagulant activity but gain antiproliferative properties against two cancer cell lines. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
凝血酶结合适体（TBA）具有抗增殖特性，但由于其同时具有抗凝活性，其潜在的发展受到阻碍。
通过 NMR 和 CD 技术研究了基于 TBA 序列（GGTTGGTGTGGTTGG）的 5 个寡核苷酸（ODN），这些 ODN 含有 l-残基或 l-残基和反转极性位点，以研究它们形成 G-四链体结构的能力。此外，还测试了它们的抗凝（PT 测定）和抗增殖特性（MTT 测定），以及它们在胎牛血清中的耐药性。
CD 和 NMR 数据表明，所研究的 ODN 能够形成右手和左手 G-四链体结构。所有 ODN 都不保留 TBA 的抗凝活性特征，但对两种癌细胞系具有显著的抗增殖活性。它们在六天后的生物环境中的耐药性因 ODN 而异。
将结果与文献数据进行比较表明，所研究的 TBA 类似物的抗增殖活性可能取决于两个因素：a）与其他已鉴定或提出的抗增殖 G-四链体适体不同的生物学途径和靶标，b）基于鸟嘌呤的降解产物的贡献。
含有 l-残基和反转极性位点的修饰 TBA 类似物失去了抗凝活性，但对两种癌细胞系具有抗增殖特性。本文是特刊“G-四链体”的一部分，客座编辑：Concetta Giancola 博士和 Daniela Montesarchio 博士。
