Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review

Ribofuranose sugar conformation plays an important role in the structure and dynamics of functional nucleic acids such as siRNAs, AONs, aptamers, miRNAs, etc. To improve their therapeutic potential, several chemical modifications have been introduced into the sugar moiety over the years. The stability of the oligonucleotide duplexes as well as the formation of stable and functional protein-oligonucleotide complexes are dictated by the conformation and dynamics of the sugar moiety. In this review, we systematically categorise various ribofuranose sugar modifications employed in DNAs and RNAs so far. We discuss different stereoelectronic effects imparted by different substituents on the sugar ring and how these effects control sugar puckering. Using this data, it would be possible to predict the precise use of chemical modifications and design novel sugar-modified nucleosides for therapeutic oligonucleotides that can improve their physicochemical properties.

Automated summary

The conformation of ribofuranose sugar is crucial for the structure and dynamics of functional nucleic acids. Different chemical modifications have been introduced to enhance their therapeutic potential and physicochemical properties. This review systematically categorizes the various ribofuranose sugar modifications used in DNAs and RNAs and discusses their effects on sugar puckering.