Synthesis and properties of 2'-O,4'-C-spirocyclopropylene bridged nucleic acid (scpBNA), an analogue of 2',4'-BNA/LNA bearing a cyclopropane ring.

Abstract

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.