Synthesis, binding, nuclease resistance and cellular uptake properties of 2'-O-acetalester-modified oligonucleotides containing cationic groups.
Bioorg Med Chem
; 23(17): 5360-8, 2015 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-26260340
ABSTRACT
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Diester Fosfórico Hidrolases
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article