Synthesis and properties of GuNA purine/pyrimidine nucleosides and oligonucleotides

Abstract

We recently designed guanidine-bridged nucleic acids (GuNA), and GuNA bearing a thymine (T) nucleobase was synthesized and successfully incorporateed into oligonucleotides. The GuNA-T-modified oligonucleotides possessed high duplex-forming ability towards their...

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

“…Among them, GuNA[Me]-A-modified ON1 exhibited a slightly lower ΔT m value than others. This type of nucleobase-dependent difference in ΔT m values is also seen in other GuNA[H]-modified oligonucleotides [25]. Since…”

“…The acetyl group was selected as a protecting group for the guanidine moiety because it can be easily removed under the basic conditions (ammonia/methylamine solution) used for the DNA synthesis [20]. The phosphoramidite synthesis was started from 2'-amino-LNAs 1a-c, which were rapidly prepared via the transglycosylations of 2'-amino-LNA-T [25]. First, the 2'-amino groups of 1a-c were converted into guanidine moieties with a methyl group using N-acetyl-S,N'-dimethylisothiourea [28], which yielded 65-83% of the products 2a-c.…”

“…The preparation of all four phosphoramidites (A, G, m C, and T) is generally not easy because each nucleobase differs in the sensitivity to reactions, and appropriate protecting groups need to be selected [8,[21][22][23]. We recently achieved the synthesis of all four GuNA[H] phosphoramidites, where transglycosylations of the 2'-amino-LNA analog with the corresponding nucleobases were performed as the key reactions [24,25]. The trans- glycosylation is a powerful strategy that simplifies the preparation of phosphoramidites at the late stages of the syntheses [26,27].…”

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

“…AMO-1 designed by us was synthesized in GeneDesign (Osaka, Japan) according to a standard protocol. The other GuNA-substituted AMOs were synthesized using standard phosphoramidite chemistry and our previously reported protocol . The GuNA-modified oligonucleotides were stable under conditions such as 1 M TBAF solution in THF at 65 °C for 8 h or 28% aqueous ammonia solution at 65 °C for 8 h, during deprotection and removal from the solid support.…”

“…Guanidine-bridged nucleic acids (GuNAs) have a high binding affinity to DNA/RNA, greatly improved nuclease resistance, high base discrimination ability, and cationic character (Figure B) . In 2018, an efficient and facile synthetic method for the preparation of 2′-amino-LNA, applicable to both purine and pyrimidine nucleosides, was developed, enabling the efficient synthesis of the adenine, guanine, cytosine, and thymine amidites. , Investigating the relationships between chemical modifications and AMO activity can help improve our understanding of their mechanisms of action and facilitate their use in the clinic. In this study, we synthesized various AMOs containing GuNAs and evaluated the relationship between the site of introduction of GuNAs and the miRNA-inhibitory activity of the molecules.…”