siRNA modified with 2′-deoxy-2′-c-methylpyrimidine nucleosides
(2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was in...
| Autores: | , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | Argentina |
| Recursos: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/98721 |
| Acesso em linha: | http://hdl.handle.net/11336/98721 |
| Access Level: | acceso abierto |
| Palavra-chave: | ACTIVITY RELATIONSHIPS DEOXYMETHYLPYRIMIDINE BASES NUCLEOSIDES SIRNA STABILITY STRUCTURE https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| Resumo: | (2′S)-2′-Deoxy-2′-C-methyluridine and (2′R)-2′-deoxy-2′-C-meth-yluridine were incorporated in the 3’-overhang region of the sense and antisense strands and in positions 2 and 5 of the seed region of siRNA duplexes directed against Renilla luciferase, whereas (2′S)-2′-deoxy-2′-C-methylcytidine was incorporated in the 6-position of the seed region of the same constructions. A dual luciferase reporter assay in transfected HeLa cells was used as a model system to measure the IC50 values of 24 different modified duplexes. The best results were obtained by the substitution of one thymidine unit in the antisense 3’-overhang region by (2′S)-or (2′R)-2′-deoxy-2′-C-methyluridine, reducing IC50 to half of the value observed for the natural control. The selectivity of the modified siRNA was measured, it being found that modifications in positions 5 and 6 of the seed region had a positive effect on the ON/OFF activity. |
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