siRNA Modified with 2-Deoxy-2-C-methylpyrimidine Nucleosides

被引：4

作者：

Dellafiore, Maria ^{[1
]}

Avino, Anna ^{[2
,3
]}

Alagia, Adele ^{[2
,3
]}

Montserrat, Javier M. ^{[4
,5
]}

Iribarren, Adolfo M. ^{[5
,6
]}

Eritja, Ramon ^{[2
,3
]}

机构：

[1] INGEBI CONICET, Vuelta Obligado 2490, RA-1428 Buenos Aires, DF, Argentina

[2] Spanish Council Sci Res CSIC, Inst Adv Chem Catalonia IQAC, Jordi Girona 18-26, Barcelona 182608034, Spain

[3] NetworkingCtr Bioengn Biomat & Nanomed CIBER BBN, Av Monforte de Lemos,3-5 Pabellon 11 Planta 0, Madrid 28029, Spain

[4] Univ Nacl Gen Sarmiento, Inst Ciencias, JM Gutierrez 1150,B1613GSX, Los Polvorines, Buenos Aires, Argentina

[5] Consejo Nacl Invest Cient & Tecn CONICET, C1425FQB, RA-2290 Buenos Aires, DF, Argentina

[6] Univ Nacl Quilmes, Lab Biotransformac, Roque Saenz Pena352, RA-1876 Buenos Aires, DF, Argentina

来源：

CHEMBIOCHEM | 2018年 / 19卷 / 13期

关键词：

deoxymethylpyrimidine bases; nucleosides; siRNA; stability; structure-activity relationships; DOUBLE-STRANDED-RNA; CHEMICAL-MODIFICATION; MAMMALIAN-CELLS; 10-23; DNAZYMES; NOBEL LECTURE; INTERFERENCE; RESISTANCE; NUCLEASES; IMPROVE; DESIGN;

D O I：

10.1002/cbic.201800077

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

(2S)-2-Deoxy-2-C-methyluridine and (2R)-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 (2S)-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 (2S)- or (2R)-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.

引用

页码：1409 / 1413

页数：5

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