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

共 28 条

[21] 9 5′-(E)-Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA-GalNAc Conjugates [J].

Parmar, Rubina ;

Willoughby, Jennifer L. S. ;

Liu, Jingxuan ;

Foster, Donald J. ;

Brigham, Benjamin ;

Theile, Christopher S. ;

Charisse, Klaus ;

Akinc, Akin ;

Guidry, Erin ;

Pei, Yi ;

Strapps, Walter ;

Cancilla, Mark ;

Stanton, Matthew G. ;

Rajeev, Kallanthottathil G. ;

Sepp-Lorenzino, Laura ;

Manoharan, Muthiah ;

Meyers, Rachel ;

Maier, Martin A. ;

Jadhav, Vasant .

CHEMBIOCHEM, 2016, 17 (11) :985-989

[22] 2-C-Methyluridine modified hammerhead ribozyme against the estrogen receptor [J].

Pontiggia, Rodrigo ;

Pontiggia, Osvaldo ;

Simian, Marina ;

Montserrat, Javier M. ;

Engels, Joachim W. ;

Iribarren, Adolfo M. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (09) :2806-2808

[23] Positional effect of chemical modifications on short interference RNA activity in mammalian cells [J].

Prakash, TP ;

Allerson, CR ;

Dande, P ;

Vickers, TA ;

Sioufi, N ;

Jarres, R ;

Baker, BF ;

Swayze, EE ;

Griffey, RH ;

Bhat, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (13) :4247-4253

[24] Rational siRNA design for RNA interference [J].

Reynolds, A ;

Leake, D ;

Boese, Q ;

Scaringe, S ;

Marshall, WS ;

Khvorova, A .

NATURE BIOTECHNOLOGY, 2004, 22 (03) :326-330

[25] Activity of Core-Modified 10-23 DNAzymes against HCV [J].

Robaldo, Laura ;

Berzal-Herranz, Alfredo ;

Montserrat, Javier M. ;

Iribarren, Adolfo M. .

CHEMMEDCHEM, 2014, 9 (09) :2172-2177

[26] Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes [J].

Robaldo, Laura ;

Izzo, Franco ;

Dellafiore, Maria ;

Proietti, Cecilia ;

Elizalde, Patricia V. ;

Montserrat, Javier M. ;

Iribarren, Adolfo M. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (08) :2581-2586

[27] Effect of North Bicyclo[3.1.0]hexane 2′-Deoxy-pseudosugars on RNA Interference: A Novel Class of siRNA Modification [J].

Terrazas, Montserrat ;

Ocampo, Sandra M. ;

Carlos Perales, Jose ;

Marquez, Victor E. ;

Eritja, Ramon .

CHEMBIOCHEM, 2011, 12 (07) :1056-1065

[28] Synthesis and properties of small interfering RNA duplexes carrying 5-ethyluridine residues [J].

Terrazas, Montserrat ;

Eritja, Ramon .

MOLECULAR DIVERSITY, 2011, 15 (03) :677-686

← 1 2 3 →