Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA Performance
Autor: | Yukiko Kamiya, Hiroyuki Asanuma, Keiji Murayama, Jumpei Ariyoshi, Yuka Donoshita, Hiroshi Kamimoto |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oligonucleotides Biology 010402 general chemistry 01 natural sciences Biochemistry Nucleobase Propanolamines 03 medical and health sciences Nucleic Acids microRNA Gene expression Humans 2-Aminopurine Molecular Biology Nuclease Oligonucleotide Organic Chemistry Chemical modification 0104 chemical sciences MicroRNAs 030104 developmental biology Propylene Glycols Nucleic acid biology.protein Molecular Medicine Function (biology) HeLa Cells |
Zdroj: | Chembiochem : a European journal of chemical biology. 18(19) |
ISSN: | 1439-7633 |
Popis: | 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. |
Databáze: | OpenAIRE |
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