8ynp

RNA duplex containing Methylformamide

spinqualitylabelsall models 8ynp, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ynp is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: 5BU, HHX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In this study, we report the synthesis of 2'-formamidonucleoside phosphoramidite derivatives and their incorporation into siRNA strands to reduce seed-based off-target effects of small interfering RNAs (siRNAs). Formamido derivatives of all four nucleosides (A, G, C and U) were synthesized in 5-11 steps from commercial compounds. Introducing these derivatives into double-stranded RNA slightly reduced its thermodynamic stability, but X-ray crystallography and CD spectrum analysis confirmed that the RNA maintained its natural A-form structure. Although the introduction of the 2'-formamidonucleoside derivative at the 2nd position in the guide strand of the siRNA led to a slight decrease in the on-target RNAi activity, the siRNAs with different sequences incorporating 2'-formamidonucleoside with four kinds of nucleobases into any position other than 2nd position in the seed region revealed a significant suppression of off-target activity while maintaining on-target RNAi activity. This indicates that 2'-formamidonucleosides represent a promising approach for mitigating off-target effects in siRNA therapeutics. Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.,Nomura K, An S, Kobayashi Y, Kondo J, Shi T, Murase H, Nakamoto K, Kimura Y, Abe N, Ui-Tei K, Abe H Nucleic Acids Res. 2024 Oct 14;52(18):10754-10774. doi: 10.1093/nar/gkae741. PMID:39231537 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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