3V06

Crystal structure of S-6'-Me-3'-fluoro hexitol nucleic acid

Summary for 3V06

• Entry DOI: 10.2210/pdb3v06/pdb
• Related: 3V07
• Descriptor: DNA (5'-D(*GP*CP*GP*TP*AP*(F5H)P*AP*CP*GP*C)-3'), STRONTIUM ION (3 entities in total)
• Functional Keywords: a-form dna, 3'-fluoro hexitol nucleic acid, fhna, s-6'-me-fhna, antisense oligonucleotides, dna
• Total number of polymer chains: 2
• Total formula weight: 6269.72

Authors

Pallan, P.S.,Egli, M. (deposition date: 2011-12-07, release date: 2012-02-08, Last modification date: 2023-09-13)

Primary citation

Pallan, P.S.,Yu, J.,Allerson, C.R.,Swayze, E.E.,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, 51:7-9, 2012

PubMed 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.

PubMed: 22229409
DOI: 10.1021/bi201810r

Experimental method

X-RAY DIFFRACTION (1.53 Å)