Introduction of 2,6‐Diaminopurines into Serinol Nucleic Acid Improves Anti‐miRNA Performance

MicroRNAs (miRNAs) are endogenous small RNAs that regulate gene expression at the post‐transcriptional level by sequence‐specific hybridisation. Anti‐miRNA oligonucleotides (AMOs) are inhibitors of miRNA activity. Chemical modification of AMOs is required to increase binding affinity and stability in serum and cells. In this study, we synthesised AMOs with our original acyclic nucleic acid, serinol nucleic acid (SNA), backbone and with the artificial nucleobase 2,6‐diaminopurine. The AMO composed of only SNA had strong nuclease resistance and blocked endogenous miRNA activity. A significant improvement in anti‐miRNA activity of the AMO was achieved by introduction of a 2,6‐diaminopurine residues into the SNA backbone. In addition, we found that the enhancement in AMO activity depended on the position of the 2,6‐diaminopurine residue in the sequence. The high potency of the SNA‐AMOs suggests that these oligomers will be useful as therapeutic reagents for control of miRNA function in patients and as tools for investigating the roles of microRNAs in cells. Finding the best position: Anti‐miRNA oligonucleotide (AMO) made by an artificial nucleic acid, serinol nucleic acid, shows remarkable nucleic‐acid resistance. Increasing the affinity to the seed and tail regions of miRNA by the introduction of 2,6‐diaminopurine into AMO improves its activity.