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Abstract:

(2'S)-2'-Deoxy-2'-C-methyluridine and (2'R)-2'-deoxy-2'-C-methyluridine 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 IC 50 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 IC 50 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. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Registro:

Documento: Artículo
Título:siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides
Autor:Dellafiore, M.; Aviñó, A.; Alagia, A.; Montserrat, J.M.; Iribarren, A.M.; Eritja, R.
Filiación:INGEBI (CONICET) Vuelta de Obligado 2490 -1428 Buenos Aires Argentina
Institute for Advanced Chemistry of Catalonia (IQAC) Spanish Council for Scientific Research (CSIC) Jordi Girona 18-26 08034 Barcelona Spain, Spain
NetworkingCenter on Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Av. Monforte de Lemos 3-5. Pabellón 11. Planta 0 Madrid 28029 Spain
Instituto de Ciencias Universidad Nacional de General Sarmiento J. M. Gutiérrez 1150 Los Polvorines B1613GSXProv. Buenos Aires Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) Godoy Cruz 2290 Buenos Aires C1425FQB Argentina
Laboratorio de Biotransformaciones Universidad Nacional de Quilmes Roque Saenz Peña352 1876 Bernal, Prov Buenos Aires Argentina
Palabras clave:Deoxymethylpyrimidine bases; Nucleosides; SiRNA; Stability; Structure-activity relationships
Año:2018
DOI: http://dx.doi.org/10.1002/cbic.201800077
Título revista:ChemBioChem
Título revista abreviado:ChemBioChem
ISSN:14394227
CODEN:CBCHF
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14394227_v_n_p_Dellafiore

Citas:

---------- APA ----------
Dellafiore, M., Aviñó, A., Alagia, A., Montserrat, J.M., Iribarren, A.M. & Eritja, R. (2018) . siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides. ChemBioChem.
http://dx.doi.org/10.1002/cbic.201800077
---------- CHICAGO ----------
Dellafiore, M., Aviñó, A., Alagia, A., Montserrat, J.M., Iribarren, A.M., Eritja, R. "siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides" . ChemBioChem (2018).
http://dx.doi.org/10.1002/cbic.201800077
---------- MLA ----------
Dellafiore, M., Aviñó, A., Alagia, A., Montserrat, J.M., Iribarren, A.M., Eritja, R. "siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides" . ChemBioChem, 2018.
http://dx.doi.org/10.1002/cbic.201800077
---------- VANCOUVER ----------
Dellafiore, M., Aviñó, A., Alagia, A., Montserrat, J.M., Iribarren, A.M., Eritja, R. siRNA Modified with 2'-Deoxy-2'-C-methylpyrimidine Nucleosides. ChemBioChem. 2018.
http://dx.doi.org/10.1002/cbic.201800077