View source for 8ynp


==RNA duplex containing Methylformamide==
<StructureSection load='8ynp' size='340' side='right'caption='[[8ynp]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ynp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8YNP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YNP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5BU:5-BROMO-URIDINE-5-MONOPHOSPHATE'>5BU</scene>, <scene name='pdbligand=HHX:[(2~{R},3~{S},4~{R},5~{R})-5-[2,4-bis(oxidanylidene)pyrimidin-1-yl]-4-[methanoyl(methyl)amino]-3-oxidanyl-oxolan-2-yl]methyl+dihydrogen+phosphate'>HHX</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ynp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ynp OCA], [https://pdbe.org/8ynp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ynp RCSB], [https://www.ebi.ac.uk/pdbsum/8ynp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ynp ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== 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<ref>PMID:39231537</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ynp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Abe H]]
[[Category: Kondo J]]