7OOS

The crystal structure of a DNA:RNA hybrid duplex sequence CTTTTCTTTG

7OOS の概要

• エントリーDOI: 10.2210/pdb7oos/pdb
• 分子名称: RNA (5'-R(*CP*AP*AP*AP*GP*AP*AP*AP*AP*G)-3'), DNA (5'-D(*CP*TP*(05K)P*TP*CP*TP*TP*TP*G)-3'), STRONTIUM ION, ... (4 entities in total)
• 機能のキーワード: amide-lna, duplex, dna:rna, unmodified, dna-rna hybrid
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6383.35

構造登録者

Thorpe, C.,Hardwick, J.,McDonough, M.A.,Hall, J.P.,Baker, Y.R.,El-Sagheer, A.H.,Brown, T. (登録日: 2021-05-28, 公開日: 2022-08-03, 最終更新日: 2024-02-07)

主引用文献

Baker, Y.R.,Thorpe, C.,Chen, J.,Poller, L.M.,Cox, L.,Kumar, P.,Lim, W.F.,Lie, L.,McClorey, G.,Epple, S.,Singleton, D.,McDonough, M.A.,Hardwick, J.S.,Christensen, K.E.,Wood, M.J.A.,Hall, J.P.,El-Sagheer, A.H.,Brown, T.
An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides.
Nat Commun, 13:4036-4036, 2022

PubMed Abstract: Oligonucleotides that target mRNA have great promise as therapeutic agents for life-threatening conditions but suffer from poor bioavailability, hence high cost. As currently untreatable diseases come within the reach of oligonucleotide therapies, new analogues are urgently needed to address this. With this in mind we describe reduced-charge oligonucleotides containing artificial LNA-amide linkages with improved gymnotic cell uptake, RNA affinity, stability and potency. To construct such oligonucleotides, five LNA-amide monomers (A, T, C, 5mC and G), where the 3'-OH is replaced by an ethanoic acid group, are synthesised in good yield and used in solid-phase oligonucleotide synthesis to form amide linkages with high efficiency. The artificial backbone causes minimal structural deviation to the DNA:RNA duplex. These studies indicate that splice-switching oligonucleotides containing LNA-amide linkages and phosphorothioates display improved activity relative to oligonucleotides lacking amides, highlighting the therapeutic potential of this technology.

PubMed: 35821218
DOI: 10.1038/s41467-022-31636-2

実験手法

X-RAY DIFFRACTION (2.6 Å)