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Title: Structural characterization and biological evaluation of small interfering RNAs containing cyclohexenyl nucleosides
Authors: Nauwelaerts, Koen ×
Fisher, Michael
Froeyen, Mathy
Lescrinier, Eveline
Van Aerschot, Arthur
Xu, Dong
DeLong, Robert
Kang, Hyumin
Juliano, Rudolph L
Herdewijn, Piet #
Issue Date: Aug-2007
Publisher: Amer chemical soc
Series Title: Journal of the American Chemical Society vol:129 issue:30 pages:9340-9348
Abstract: CeNA is an oligonucleotide where the (deoxy)ribose sugars have been replaced by cyclohexenyl moieties. We have determined the NMR structure of a CeNA:RNA duplex and have modeled this duplex in the crystal structure of a PIWI protein. An N puckering of the ribose nucleosides, a H-2(3) conformation of the cyclohexenyl nucleosides, and an A-like helix conformation of the backbone, which deviates from the standard A-type helix by a larger twist and a smaller slide, are observed. The model of the CeNA:RNA duplex bound to the PIWI protein does not show major differences in the interaction of the guide CeNA with the protein when compared with dsRNA, suggesting that CeNA modified oligonucleotides might be useful as siRNAs. Incorporation of one or two CeNA units in the sense or antisense strands of dsRNA led to similar or enhanced activity compared to unmodified siRNAs. This was tested by targeting inhibition of expression of the MDR1 gene with accompanying changes in P-glycoprotein expression, drug transport, and drug resistance.
ISSN: 0002-7863
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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