Brodyagin Nikita, Katkevics Martins, Kotikam Venubabu, Ryan Christopher A, Rozners Eriks
Department of Chemistry, Binghamton University, The State University of New York, Binghamton, New York 13902, United States.
Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia.
Beilstein J Org Chem. 2021 Jul 19;17:1641-1688. doi: 10.3762/bjoc.17.116. eCollection 2021.
Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA's chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA's binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA's binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications.
肽核酸（PNA）可以说是最成功的DNA模拟物之一，尽管它与DNA的天然结构有很大差异。本综述总结了30年来关于PNA的化学、结构和功能优化、作为探针和诊断工具的应用以及开发新型PNA疗法的研究。讨论首先简要回顾了PNA的结合模式和结构特征，接着介绍了最具影响力的化学修饰、基于PNA的检测和诊断方法，并讨论了PNA疗法的当前发展状况。虽然许多修饰提高了PNA的结合亲和力和特异性、溶解度及其他生物物理性质，但原始的PNA仍最常用于诊断和其他体外应用。PNA疗法及其他体内应用的开发明显滞后，仍受生物利用度不足和组织特异性递送困难的限制。需要相对高剂量来克服细胞摄取不良和内体截留问题，这增加了毒性风险。这些限制仍是有待解决的问题，等待创新的化学和生物学方法来释放PNA在生物医学应用中的全部潜力。
