2g92: Difference between revisions
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[[ | ==Crystal Structure Analysis of the RNA Dodecamer CGC-(NF2)-AAUUAGCG, with an Incorporated 2,4-Difluorotoluyl Residue (NF2)== | ||
<StructureSection load='2g92' size='340' side='right' caption='[[2g92]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2g92]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G92 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2G92 FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NF2:(1S)-1,4-ANHYDRO-1-(2,4-DIFLUORO-5-METHYLPHENYL)-5-O-PHOSPHONO-D-RIBITOL'>NF2</scene></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=2g92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g92 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2g92 RCSB], [http://www.ebi.ac.uk/pdbsum/2g92 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recently, chemically synthesized short interfering RNA (siRNA) duplexes have been used with success for gene silencing. Chemical modification is desired for therapeutic applications to improve biostability and pharmacokinetic properties; chemical modification may also provide insight into the mechanism of silencing. siRNA duplexes containing the 2,4-difluorotoluyl ribonucleoside (rF) were synthesized to evaluate the effect of noncanonical nucleoside mimetics on RNA interference. 5'-Modification of the guide strand with rF did not alter silencing relative to unmodified control. Internal uridine to rF substitutions were well-tolerated. Thermal melting analysis showed that the base pair between rF and adenosine (A) was destabilizing relative to a uridine-adenosine pair, although it was slightly less destabilizing than other mismatches. The crystal structure of a duplex containing rFoA pairs showed local structural variations relative to a canonical RNA helix. As the fluorine atoms cannot act as hydrogen bond acceptors and are more hydrophobic than uridine, there was an absence of a well-ordered water structure around the rF residues in both grooves. siRNAs with the rF modification effectively silenced gene expression and offered improved nuclease resistance in serum; therefore, evaluation of this modification in therapeutic siRNAs is warranted. | |||
Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide.,Xia J, Noronha A, Toudjarska I, Li F, Akinc A, Braich R, Frank-Kamenetsky M, Rajeev KG, Egli M, Manoharan M ACS Chem Biol. 2006 Apr 25;1(3):176-83. PMID:17163665<ref>PMID:17163665</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Egli, M.]] | [[Category: Egli, M.]] | ||
[[Category: Li, F.]] | [[Category: Li, F.]] | ||
Revision as of 15:28, 12 October 2014
Crystal Structure Analysis of the RNA Dodecamer CGC-(NF2)-AAUUAGCG, with an Incorporated 2,4-Difluorotoluyl Residue (NF2)
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