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Synthesis and properties of small interfering RNA duplexes carrying 5-ethyluridine residues

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Abstract

Oligoribonucleotides carrying 5-ethyluridine units were prepared using solid-phase phosphoramidite chemistry. The introduction of the tert-butyldimethylsilyl group at the 2′-OH position proceeded in good yield and very high 2′-regioselectivity. RNA duplexes carrying 5-ethyluridine either at the sense or the guide strands display RNAi activity comparable to or slightly better than that of unmodified RNA duplexes. Gene suppression experiments using luciferase targets in SH-SY5Y cells show that the ethyl group is generally well accepted at all positions although a small decrease in RNA interference activity is observed when one 5-ethylU residue is incorporated in the 3′ overhangs.

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Abbreviations

as:

Guide (antisense) strand

ACN:

Acetonitrile

DIPEA:

N,N-diisopropylethylamine

DMAP:

N,N-dimethylaminopyridine

DMEM:

Dulbecco’s modified Eagle medium

DMT:

4,4′-Dimethoxytrityl

EtOAc:

Ethyl acetate

FBS:

Fetal bovine serum

HEPES:

4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid

MeOH:

Methanol

siRNA:

Small interfering RNA

ss:

Sense strand

TBAF:

Tetrabutylammonium fluoride

TBDMS:

tert-Butyldimethylsilyl

TEAA:

Triethylammonium acetate

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Authors and Affiliations

  1. Institute for Research in Biomedicine (IRB Barcelona), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Baldiri i Reixac 10, 08028, Barcelona, Spain

    Montserrat Terrazas & Ramon Eritja

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  1. Montserrat Terrazas
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  2. Ramon Eritja
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Correspondence to Ramon Eritja.

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Terrazas, M., Eritja, R. Synthesis and properties of small interfering RNA duplexes carrying 5-ethyluridine residues. Mol Divers 15, 677–686 (2011). https://doi.org/10.1007/s11030-010-9290-1

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