# Synthesis and structural analysis of dinucleotides containing 2′,3′-trans-bridged nucleic acids with trans-5,6- or 5,7-fused ring skeleton

## TL;DR

Researchers designed and synthesized new artificial nucleic acids with a modified sugar structure that can form stable DNA-like structures.

## Contribution

The synthesis and structural analysis of dinucleotides with 2′,3′-trans-BNA sugar modifications is presented.

## Key findings

- 2′,3′-trans-BNAs were synthesized using a gold-catalyzed cyclization reaction from a glucose derivative.
- The sugar conformation of 2′,3′-trans-BNAs is N-type, similar to RNA-duplex but with distinct torsion angles ζ and α.

## Abstract

Artificial nucleic acids in which the conformation of the sugar or phosphate backbone of the oligonucleotide is appropriately fixed can form stable duplexes. In this study, we designed dinucleotides containing 2′,3′-trans-bridged nucleic acids (2′,3′-trans-BNAs) based on the idea that the sugar conformation and torsions angles δ, ε, ζ, α, and β of the backbone can be controlled by a 5,6- or 5,7-membered trans-fused ring skeleton cyclized between the 2′- and 3′-positions of the sugar moiety. Given that the construction of trans-5,6-fused ring skeletons is synthetically challenging, the synthesis was optimized and a detailed structural analysis of these new bridged 2′,3′-trans-BNA systems was conducted. The 2′,3′-trans-BNAs could be synthesized from a commercially available d-glucose derivative with the key intramolecular gold-catalyzed cyclization reaction achieved using a cyclization precursor bearing an intramolecular hydroxy group and an internal alkyne. Structural analysis of the 2′,3′-trans-BNAs showed an N-type sugar conformation for all the derivatives, which is similar to that in RNA-duplex, and the ζ and α torsion angles for the 2′,3′-trans-BNAs were a characteristic feature of the compounds that differ from the corresponding angles of the natural duplexes.

Artificial nucleic acids with a fixed conformation of the backbone of the oligonucleotide can form stable duplexes, however, the synthesis of modified nucleotides with non-canonical three-dimensional structures remains very challenging. Here, the authors design and synthesize dinucleotides containing 2′,3′-trans-bridged nucleic acids (2′,3′-trans-BNAs), showing a similar N-type sugar conformation in RNA-duplex but with different ζ and α torsion angles.