Synthesis and properties of 2′-O,4′-C-spirocyclopropylene bridged nucleic acid (scpBNA), an analogue of 2′,4′-BNA/LNA bearing a cyclopropane ringElectronic supplementary information (ESI) available: Full experimental details, 1H, 13C, and 31P NMR spectra of all new compounds, HPLC charts and MALDI-TOF-MS spectra of new oligonucleotides, UV melting profiles for representative oligonucleotides, HPLC data of nuclease experiments, mismatch discrimination data, thermodynamic data and van't Hoff plots

• Main Authors: Yamaguchi, Takao, Horiba, Masahiko, Obika, Satoshi
• Format: Journal Article
• Language: English
• Published: 28.05.2015
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c5cc02024g

2′- O ,4′- C -Spirocyclopropylene bridged nucleic acid (scpBNA), an analogue of 2′- O ,4′- C -methylene bridged nucleic acid (2′,4′-BNA/LNA) bearing a cyclopropane ring at the 6′-position, was synthesized and successfully incorporated into oligonucleotides. The scpBNA-modified oligonucleotides showed excellent duplex-forming ability with complementary single-stranded RNA and exhibited increased enzymatic stability as compared to the corresponding natural and 2′,4′-BNA/LNA-modified oligonucleotides. Our results demonstrate the potential of scpBNA for gene therapeutics, such as antisense technology. The scpBNA-modified oligonucleotides exhibit excellent duplex-forming ability toward the complementary ssRNA, and dramatically increased resistance to nuclease activity compared to their 2′,4′-BNA/LNA-modified counterparts.