Structural highlights
Publication Abstract from PubMed
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.
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.,Pallan PS, Yu J, Allerson CR, Swayze EE, Seth P, Egli M Biochemistry. 2012 Jan 10;51(1):7-9. Epub 2011 Dec 29. PMID:22229409[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pallan PS, Yu J, Allerson CR, Swayze EE, Seth P, Egli M. 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. Biochemistry. 2012 Jan 10;51(1):7-9. Epub 2011 Dec 29. PMID:22229409 doi:10.1021/bi201810r
