6bgb

<StructureSection load='6bgb' size='340' side='right' caption='[[6bgb]], [[Resolution|resolution]] 1.65&Aring;' scene=''>

<table><tr><td colspan='2'>[[6bgb]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BGB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BGB FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7C:'>A7C</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nfo|4nfo]], [[4nfp|4nfp]], [[4nfq|4nfq]]</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bgb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bgb OCA], [http://pdbe.org/6bgb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bgb RCSB], [http://www.ebi.ac.uk/pdbsum/6bgb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bgb ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

SiRNAs can cause unintended gene silencing due to miRNA-like effects because of the similarity in function of an siRNA guide strand and a miRNA. Here we evaluate the effect on miRNA-like off targeting of introducing the adenosine derivative 7-EAA and triazoles prepared from 7-EAA at different positions in an siRNA guide strand. We find that a sterically demanding triazole placed in the RNA duplex major groove at position six of the guide strand dramatically reduces miRNA-like off targeting potency. A high-resolution structure of an RNA duplex bearing a novel, major-groove localized triazole is reported, which suggests that modified triazoles could be disrupting the hAgo2-guide-target RNA ternary complex. Five different triazole modifications were tested at the guide strand 6-position for effects on on-target and miRNA-like off target knockdown potency. A 7-EAA triazole bearing a benzylamine substituent displayed on-target knockdown activity as potent as the native siRNA, while having an IC50 against a miRNA-like off target &gt;100-fold higher. Melting temperature studies revealed no obvious correlation between potency in knockdown assays and a modification's effect on duplex stability. These results, along with known structures of hAgo2-guide-target ternary complexes, are used to rationalize the effect of 7-EAA triazoles on miRNA-like off target effects.

Controlling miRNA-like off-target effects of an siRNA with nucleobase modifications.,Suter SR, Ball-Jones A, Mumbleau MM, Valenzuela R, Ibarra-Soza J, Owens H, Fisher AJ, Beal PA Org Biomol Chem. 2017 Nov 22. doi: 10.1039/c7ob02654d. PMID:29164215<ref>PMID:29164215</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6bgb" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Beal, P A]]

[[Category: Fisher, A J]]

[[Category: Mumbleau, M M]]

[[Category: Duplex]]

[[Category: Rna]]

[[Category: Synthetic]]