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.