Structure–Activity Relationships of Anti-microRNA Oligonucleotides Containing Cationic Guanidine-Modified Nucleic Acids

Anti-microRNA oligonucleotides (AMOs) are valuable tools for the treatment of diseases caused by the dysregulation of microRNA expression. However, the correlation between chemical modifications in AMO sequences and the microRNA-inhibitory activity has not been fully elucidated. In this study, we synthesized a series of AMOs containing cationic guanidine-bridged nucleic acids (GuNA) and evaluated their activities using a dual luciferase assay. We also optimized the site of GuNA substitution and found an effective design for the inhibition of microRNA-21, which was partially different from that of conventional nucleic acid derivatives. This study showed that GuNA-substituted AMOs are effective in inhibiting the function of microRNA.抗微小RNA寡核苷酸（Anti-microRNA oligonucleotides，AMOs）是一类可用于治疗因微小RNA表达失调引发疾病的宝贵工具。然而，AMO序列中的化学修饰与其抗微小RNA活性之间的关联尚未完全阐明。本研究中，我们合成了一系列携带有阳离子胍桥核酸（cationic guanidine-bridged nucleic acids，GuNA）的AMO，并通过双荧光素酶测定法评估其活性。我们还对GuNA的取代位点进行了优化，找到了可有效抑制微小RNA-21的设计方案，该方案与常规核酸衍生物的设计思路存在部分差异。本研究证实，经GuNA修饰的AMO可有效抑制微小RNA的功能。