2G92

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

2G92 の概要

• エントリーDOI: 10.2210/pdb2g92/pdb
• 分子名称: 5'-R(*CP*GP*CP*(NF2)P*AP*AP*UP*UP*AP*GP*CP*G)-3' (2 entities in total)
• 機能のキーワード: 2, 4-difluorotoluyl nucleoside, chemical modification, rna, rna interference, hydrogen bonding
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7656.71

構造登録者

Egli, M.,Li, F. (登録日: 2006-03-04, 公開日: 2006-04-18, 最終更新日: 2024-04-03)

主引用文献

Xia, J.,Noronha, A.,Toudjarska, I.,Li, F.,Akinc, A.,Braich, R.,Frank-Kamenetsky, M.,Rajeev, K.G.,Egli, M.,Manoharan, M.
Gene silencing activity of siRNAs with a ribo-difluorotoluyl nucleotide.
Acs Chem.Biol., 1:176-183, 2006

PubMed Abstract: 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.

PubMed: 17163665
DOI: 10.1021/cb600063p

実験手法

X-RAY DIFFRACTION (1.61 Å)