Thermostability Trends of TNA:DNA Duplexes Reveal Strong Purine Dependence
Thermostability Trends of TNA:DNA Duplexes Reveal Strong Purine Dependence
复制标题
DOI：
10.1021/acssynbio.9b00028
复制
发表时间：
2019-05-01
影响因子：
4.7
通讯作者：
Heemstra, Jennifer M.
中科院分区：
文献类型：
--
作者：
Lackey, Hershel H.;Peterson, Eric M.;Heemstra, Jennifer M.
高保真聚合酶的发展和流线型的苏阿糖核酸的合成(TNA)三磷酸腺苷和phosphoramidites使得TNA访问主题生成的高亲和性寡核苷酸适配子nuclease-resistant,反义寡核苷酸,合成基因生物聚合物。然而，对TNA:DNA双链的热稳定性趋势知之甚少。在这里，我们研究了14种TNA:DNA双链的热稳定性，目的是阐明控制TNA:DNA双链稳定性的基本因素。我们发现TNA中的嘌呤含量显著影响TNA:DNA双链的稳定性和构象。低TNA嘌呤含量会破坏双链的稳定性，其T-m值通常比类似的DNA:DNA和RNA:DNA双链低5摄氏度。相比之下，具有高TNA嘌呤含量的TNA:DNA双链比具有相同序列的DNA:DNA或RNA:DNA双链表现出更大的稳定性。高TNA嘌呤含量导致TNA:DNA双链采用类似RNA:RNA （A-form）的构象，而低TNA嘌呤含量的双链具有更类似DNA:DNA （B-form）的构象。这些见解为理解和预测TNA:DNA双工稳定性提供了基础，有望指导TNA在生物技术应用中的实际应用。
The development of high fidelity polymerases and streamlined synthesis of threose nucleic acid (TNA) triphosphates and phosphoramidites has made TNA accessible as a motif for generating nuclease-resistant high-affinity aptamers, antisense oligos, and synthetic genetic biopolymers. Little is known, however, about the thermostability trends of TNA:DNA duplexes. Here we investigate the thermostability of 14 TNA:DNA duplexes with the goal of elucidating the fundamental factors governing TNA:DNA duplex stability. We find that purine content in TNA significantly influences the stability and conformation of TNA:DNA duplexes. Low TNA purine content destabilizes duplexes, with T-m values often 5 degrees C lower than analogous DNA:DNA and RNA:DNA duplexes. By contrast, TNA:DNA duplexes having high TNA purine content display greater stability than DNA:DNA or RNA:DNA duplexes having the same sequences. High TNA purine content leads TNA:DNA duplexes to adopt conformations similar to RNA:RNA (A-form) configuration, whereas duplexes with low TNA purine content have conformations more similar to DNA:DNA (B-form) configuration. These insights provide a basis for understanding and predicting TNA:DNA duplex stability, which is anticipated to guide the practical use of TNA in biotechnology applications.