Insights from Crystal Structures into the Opposite Effects on RNA Affinity Caused by the S- and R-6′-Methyl Backbone Modifications of 3′-Fluoro Hexitol Nucleic Acid
- 23 December 2011
- journal article
- other
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 51 (1) , 7-9
Abstract
Locked nucleic acid (LNA) analogues with 2′,4′-bridged sugars show promise in antisense applications. S-5′-Me-LNA has high RNA affinity, and modified oligonucleotides show weakened immune stimulation in vivo. Conversely, an R-5′-methyl group dramatically lowers RNA affinity. To test the effects of S- and R-6′-methyl groups on 3′-fluoro hexitol nucleic acid (FHNA) stability, we synthesized S- and R-6′-Me-FHNA thymidine and incorporated them into oligo-2′-deoxynucleotides. As with LNA, S-6′-Me is stabilizing whereas R-6′-Me is destabilizing. Crystal structures of 6′-Me-FHNA-modified DNAs explain the divergent consequences for stability and suggest convergent origins of these effects by S- and R-6′-Me (FHNA) [-5′-Me (LNA and RNA)] substituents.Keywords
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