6bgb: Difference between revisions
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==Crystal Structure of the 16mer GCAGNCUUAAGUCUGC containing BrPh 7-triazolyl-8-aza-7-deazaadenosine== | |||
<StructureSection load='6bgb' size='340' side='right' caption='[[6bgb]], [[Resolution|resolution]] 1.65Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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 >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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Mumbleau, M | <div class="pdbe-citations 6bgb" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beal, P A]] | |||
[[Category: Fisher, A J]] | |||
[[Category: Mumbleau, M M]] | |||
[[Category: Duplex]] | |||
[[Category: Rna]] | |||
[[Category: Structural classification]] | |||
[[Category: Synthetic]] | |||
Revision as of 07:25, 6 December 2017
Crystal Structure of the 16mer GCAGNCUUAAGUCUGC containing BrPh 7-triazolyl-8-aza-7-deazaadenosine
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