7ooo | pdb_00007ooo

The crystal structure of a DNA:RNA hybrid duplex sequence CTTTTCTTTG containing an LNA-Amide-LNA modification

spinqualitylabelsall models 7ooo, resolution 2.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ooo is a 4 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides.,Baker YR, Thorpe C, Chen J, Poller LM, Cox L, Kumar P, Lim WF, Lie L, McClorey G, Epple S, Singleton D, McDonough MA, Hardwick JS, Christensen KE, Wood MJA, Hall JP, El-Sagheer AH, Brown T Nat Commun. 2022 Jul 12;13(1):4036. doi: 10.1038/s41467-022-31636-2. PMID:35821218 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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