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Article Dans Une Revue Bioorganic and Medicinal Chemistry Letters Année : 2015

Synthesis, binding, nuclease resistance and cellular uptake properties of 2′- O -acetalester-modified oligonucleotides containing cationic groups

Résumé

We report on the synthesis and properties of oligonucleotides (ONs) with 2'-O-acetalester modifications containing cationic side chains in a prodrug-like approach. In the aim to improve cell penetration and nuclease resistance, various different amino- or guanidino-acetalester were grafted to 2'-OH of uridine and the corresponding phosphoramidites were incorporated into ONs. Introduction of 2'-O-(2-aminomethyl-2-ethyl)butyryloxymethyl (AMEBuOM) modification into 2'-OMe ONs leads to high resistance towards enzymatic degradation and to destabilization of duplexes with complementary RNA strand. Spontaneous uptake experiments of a twelve-mer containing ten 2'-O-AMEBuOM-U units into A673 cells showed moderate internalization of ON within the cells whereas substantial internalization of the corresponding lipophilic 2'-O-pivaloyloxymethyl ON was observed for the first time.

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Chimie
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Dates et versions

hal-03554637 , version 1 (03-02-2022)

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Annabelle Biscans, Sonia Rouanet, Jean-Rémi Bertrand, Jean-Jacques Vasseur, Christelle Dupouy, et al.. Synthesis, binding, nuclease resistance and cellular uptake properties of 2′- O -acetalester-modified oligonucleotides containing cationic groups. Bioorganic and Medicinal Chemistry Letters, 2015, 23 (17), pp.5360-5368. ⟨10.1016/j.bmc.2015.07.054⟩. ⟨hal-03554637⟩
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