Synthetic Method for 2′-Amino-LNA Bearing Any of the Four Nucleobases via a Transglycosylation Reaction

Abstract

A transglycosylation reaction of 2'-amino-locked nucleic acid (LNA) from thymine (T) to other nucleobases adenine (A), guanine (G), and 5-methylcytosine (C) has been developed. This reaction proceeds in high yield and with high β-selectivity. The mild reaction conditions enable the coexistence of acid-labile protecting groups, including a 4,4'-dimethoxytrytyl (DMTr) group. 2'-Amino-LNAs bearing any nucleobase can now be easily synthesized.

Polyamine‐Functionalized 2′‐Amino‐LNA in Oligonucleotides: Facile Synthesis of New Monomers and High‐Affinity Binding towards ssDNA and dsDNA

“…Thiss trategy circumvents the laborious synthesis of individual 2'-amino-LNA phosphoramidite monomers. Moreover,S awamoto et al recently reported an efficient method for high-yielding transglycosylationr eactions for nucleobase interconversions on the 2'amino-LNA scaffold, [38] with potential for furthere xpansion of the proposed strategy to 2'-amino-LNA monomers of all canonical nucleobases. Thus, the developedm ethod may greatly improvet he availability of ONsc arrying ar ange of 2'-amino-LNA derivatives.…”

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

“…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.…”

Parallel synthesis of oligonucleotides containing N-acyl amino-LNA and their therapeutic effects as anti-microRNAs

“…Recently, we developed a practical synthetic method for the preparation of the ALNA scaffold that is applicable to both purine and pyrimidine monomers. 37 The synthesis of phosphoramidites of appropriately protected ALNAs with A, T, G, and mC will enable further investigation of the practical utility of ALNAs in nucleic acid therapeutics. Additionally, recent studies have shown that even simple substitutions have significant effects on the pharmacokinetic and biophysical properties of therapeutic ASOs.…”