Influence of Sugar Modifications on the Nucleoside Conformation and Oligonucleotide Stability: A Critical Review
Authors:
- 1 September 2022
- journal article
- review article
- Published by Wiley in The Chemical Record
- Vol. 22 (12) , e202200174
Abstract
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.Keywords
This publication has 202 references indexed in Scilit:
- 2′-Azido RNA, a Versatile Tool for Chemical Biology: Synthesis, X-ray Structure, siRNA Applications, Click LabelingACS Chemical Biology, 2012
- An Exocyclic Methylene Group Acts As a Bioisostere of the 2′-Oxygen Atom in LNAJournal of the American Chemical Society, 2010
- Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward GlanceChemistry & Biodiversity, 2010
- A conformational transition in the structure of a 2′-thiomethyl-modified DNA visualized at high resolutionChemical Communications, 2009
- Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stabilityNucleic Acids Research, 2009
- Insights into structure, dynamics and hydration of locked nucleic acid (LNA) strand-based duplexes from molecular dynamics simulationsNucleic Acids Research, 2008
- 2′-Fluoro-4′-thioarabino-modified oligonucleotides: conformational switches linked to siRNA activityNucleic Acids Research, 2007
- Synthesis of a 2‘-Se-thymidine Phosphoramidite and Its Incorporation into Oligonucleotides for Crystal Structure StudyOrganic Letters, 2007
- Selenium derivatization of nucleic acids for crystallographyNucleic Acids Research, 2006
- Synthesis and properties of 4'-ThioDNA: unexpected RNA-like behavior of 4'-ThioDNANucleic Acids Research, 2006