(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.
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 |