Synthesis of Oligonucleotides Containing 2′-<i>N</i>-alkylaminocarbonyl-2′-amino-LNA (2′-urea-LNA) Moieties Using Post-Synthetic Modification Strategy
oleh: Shoko Yamashita, Kodai Nishida, Takashi Osawa, Ayumi Nakanishi, Yuta Ito, Yoshiyuki Hari
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2020-01-01 |
Deskripsi
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′-<i>N</i>-pentafluorophenoxycarbonyl-2′-amino-LNA, which was introduced into oligonucleotides. Oligonucleotides containing a 2′-<i>N</i>-pentafluorophenoxycarbonyl-2′-amino-LNA unit could be isolated under ultra-mild deprotection conditions (50 mM K<sub>2</sub>CO<sub>3</sub> 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′-<i>N</i>-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.