Title: The biolabile 2'-O-pivaloyloxymethyl modification in an RNA helix: an NMR solution structure
Authors: Baraguey, Carine
Lescrinier, Eveline
Lavergne, Thomas
Debart, Françoise
Herdewijn, Piet
Vasseur, Jean-Jacques # ×
Issue Date: Apr-2013
Publisher: Royal Society of Chemistry
Series Title: Organic & biomolecular chemistry vol:11 issue:16 pages:2638-2647
Abstract: The pivaloyloxymethyl (PivOM) group is a biolabile 2'-O-ribose protection that is under development in a prodrug-based approach for siRNA applications. Besides an expected cellular uptake, nucleic acid sequences carrying PivOM showed also increased nuclease resistance and, in most cases, an affinity for complementary RNA. The r(CGCU*ACGC)dT:r(GCGUAGCG)dT model duplex containing a single modified residue (U*) was synthesized and its solution structure was determined by NMR. The duplex showed a maintained A-RNA helix. In U*, both 2'-O-acetal ester side chain and ring pucker presented a notable rigid conformation. The PivOM moiety was oriented with the carbonyl group turned outside the minor groove and with trans, -ac and -ac torsion angles around the C2'-O2', O2'-CA and CA-OB1 bonds respectively. Gauche effects and dipolar interactions between the PivOM and the backbone appeared to be the predominant factors influencing the PivOM conformation and the orientation of the two supplementary H acceptors suggested that hydration could also play a role in the duplex stability.
ISSN: 1477-0520
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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