Synthesis and evaluation of a novel 2',5'-bridged nucleic acid with sugar conformation fixed to S-type by N-Olinkage

Abstract

Our work involves the design and synthesis of various types of bridged nucleic acid (BNA). Here, we describe a novel 2'-O, 5'-N-bridged nucleic acid, 2',5'-BNA(ON), whose sugar puckering is fixed to the S-type conformation by N-O linkage. A 2',5'-BNA(ON)-containing dimer unit was synthesized via a coupling reaction between a protected 2',5'-BNA(ON)-U monomer and a thymidine derivative. Introduction of 2',5'-BNA(ON)-U into DNA was carried out using conventional phosphoramidite chemistry with a DNA synthesizer. The hybridization abilities of 2',5'-BNA(ON)-U-modified oligonucleotides with their DNA or RNA complements were evaluated.