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Open AccessArticle

Synthesis of Oligonucleotides Containing 2′-N-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) Moieties Using Post-Synthetic Modification Strategy

1
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima 770-8514, Japan
2
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2020, 25(2), 346; https://doi.org/10.3390/molecules25020346
Received: 23 December 2019 / Revised: 10 January 2020 / Accepted: 14 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Recent Development of Nucleic Acid Analogs)
The post-synthetic modification of an oligonucleotide is a powerful strategy for the synthesis of various analogs of the oligonucleotide, aiming to achieve the desired functions. In this study, we synthesized the thymidine phosphoramidite of 2′-N-pentafluorophenoxycarbonyl-2′-amino-LNA, which was introduced into oligonucleotides. Oligonucleotides containing a 2′-N-pentafluorophenoxycarbonyl-2′-amino-LNA unit could be isolated under ultra-mild deprotection conditions (50 mM K2CO3 in MeOH at room temperature for 4 h). Moreover, by treatment with various amines as a post-synthetic modification, the oligonucleotides were successfully converted into the corresponding 2′-N-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) derivatives. The duplex- and triplex-forming abilities of the synthesized oligonucleotides were evaluated by UV-melting experiments, which showed that 2′-urea-LNAs could stabilize the nucleic acid complexes, similar to the proto-type, 2′-amino-LNA. Thus, 2′-urea-LNAs could be promising units for the modification of oligonucleotides; the design of a substituent on urea may aid the formation of useful oligonucleotides. In addition, pentafluorophenoxycarbonyl, an amino moiety, acted as a precursor of the substituted urea, which may be applicable to the synthesis of oligonucleotide conjugates. View Full-Text
Keywords: bridged nucleic acid; post-synthetic modification; modified oligonucleotides; 2′-urea-LNA; UV-melting experiment bridged nucleic acid; post-synthetic modification; modified oligonucleotides; 2′-urea-LNA; UV-melting experiment
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Yamashita, S.; Nishida, K.; Osawa, T.; Nakanishi, A.; Ito, Y.; Hari, Y. Synthesis of Oligonucleotides Containing 2′-N-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) Moieties Using Post-Synthetic Modification Strategy. Molecules 2020, 25, 346.

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