Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong SAR, P. R. China.
Key Laboratory of Biochip Technology, Biotech and Health Care, Shenzhen Research Institute of City University of Hong Kong, 518057, Shenzhen, P. R. China.
Chem Commun (Camb). 2024 Oct 15;60(83):11864-11889. doi: 10.1039/d4cc04443f.
This feature article delves into the realm of α-L-threose nucleic acid (TNA), an artificial nucleic acid analog characterized by a backbone comprising an unconventional four-carbon sugar, α-L-threose, with phosphodiester linkages connecting at the 2' and 3' vicinal positions of the sugar ring. Within this article, we encapsulate the potential, progress, current state of the art, and persisting challenges within TNA research. Kicking off with a historical overview of xeno nucleic acids (XNAs), the discussion transitions to the compelling attributes and structure-property relationships of TNAs as advanced tools when contrasted with natural nucleic acids. Noteworthy aspects such as their advantageous spatial arrangements of functional groups around the sugar ring, stable Watson-Crick base pairing, high binding affinity, biostability, biocompatibility, and bio-safety are highlighted. Moreover, the narrative unfolds the latest advancements in chemical and biological methodologies for TNA synthesis, spanning from monomer and oligomer synthesis to polymerization, alongside cutting-edge developments in enzyme engineering aimed at bolstering large-scale TNA synthesis for selection initiatives. The article sheds light on the evolution of TNA aptamers over time, expounding on the tools and selection techniques engineered to unearth superior binding aptamers and TNA catalysts. Furthermore, the article accentuates the recent applications of TNAs across diverse domains such as molecular detection, immunotherapy, gene therapy, synthetic biology, and molecular computing. In conclusion, we summarize the key aspects of recent TNA research, address persisting gaps and challenges, and provide crucial insights and future perspectives in the dynamic domain of TNA research.
这篇专题文章深入探讨了α-L- threose 核酸（TNA）的领域，它是一种人工核酸类似物，其骨架由非常规的四碳糖α-L- threose 组成，磷酸二酯键连接在糖环的 2'和 3'邻位。在本文中，我们总结了 TNA 研究中的潜力、进展、现状和持续挑战。从异核酸（XNAs）的历史概述开始，讨论转向了 TNA 的引人注目的属性和结构-性质关系，将其作为与天然核酸相比的先进工具。值得注意的方面包括其糖环周围功能基团的有利空间排列、稳定的 Watson-Crick 碱基配对、高结合亲和力、生物稳定性、生物相容性和生物安全性。此外，本文还阐述了 TNA 合成的化学和生物学方法的最新进展，从单体和寡聚物合成到聚合，以及酶工程的最新进展，旨在为选择计划增强大规模 TNA 合成。文章还阐述了 TNA 适体随时间的演变，介绍了用于发现具有优越结合亲和力的适体和 TNA 催化剂的工具和选择技术。此外，本文还强调了 TNA 在分子检测、免疫疗法、基因治疗、合成生物学和分子计算等多个领域的最新应用。总之，我们总结了最近 TNA 研究的关键方面，讨论了持续存在的差距和挑战，并提供了在 TNA 研究这一动态领域中的重要见解和未来展望。
