2g92

Crystal Structure Analysis of the RNA Dodecamer CGC-(NF2)-AAUUAGCG, with an Incorporated 2,4-Difluorotoluyl Residue (NF2)

spinqualitylabelsall models 2g92, resolution 1.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2g92 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: NF2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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