2-C-Methyluridine modified hammerhead ribozyme against the estrogen receptor

被引:8
作者
Pontiggia, Rodrigo [1 ]
Pontiggia, Osvaldo [2 ]
Simian, Marina [2 ]
Montserrat, Javier M. [1 ,3 ]
Engels, Joachim W. [4 ]
Iribarren, Adolfo M. [1 ,5 ]
机构
[1] Consejo Nacl Invest Cient & Tecn, INGEBI, RA-1428 Buenos Aires, DF, Argentina
[2] UBA, Inst Oncol AH Roffo, Caba, Argentina
[3] Univ Nacl Gral Sarmiento, Inst Ciencias, Prov De Bs As, Argentina
[4] Goethe Univ Frankfurt, Inst Organ Chem & Chem Biol, D-60438 Frankfurt, Germany
[5] Univ Nacl Quilmes, Lab Biotransformac, RA-1876 Bemal, Prov De Bs As, Argentina
关键词
2 '-C-methyluridine; Modified ribozyme; Estrogen receptor alpha; RNA; 2'-C-METHYLURIDINE; GLUCOSE;
D O I
10.1016/j.bmcl.2010.03.060
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A new synthesis of 2'-C-methyluridine phosphoramidite is presented. Special emphasis is dedicated to the improvement of the protection of the tertiary 2'-hydroxyl group. Comparison to previous protecting strategies and analysis of stability under 5'-DMTr removing conditions are discussed. The synthetic incorporation of this modified nucleoside into the catalytic core of a hammerhead ribozyme against the estrogen receptor alpha protein (ER-alpha), and transfection experiments in MCF-7 cell line are also presented. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2806 / 2808
页数:3
相关论文
共 18 条
[1]  
ALHUSAINI AH, 1985, J ORG CHEM, V50, P2597
[2]  
BEIGELMAN L, 1995, NUCLEIC ACIDS RES, V23, P4434
[3]   NEW SYNTHESES OF 2'-C-METHYLNUCLEOSIDES STARTING FROM D-GLUCOSE AND D-RIBOSE [J].
BEIGELMAN, LN ;
ERMOLINSKY, BS ;
GURSKAYA, GV ;
TSAPKINA, EN ;
KARPEISKY, MY ;
MIKHAILOV, SN .
CARBOHYDRATE RESEARCH, 1987, 166 (02) :219-232
[4]   Chemical modification: the key to clinical application of RNA interference? [J].
Corey, David R. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :3615-3622
[5]   Activity and stability of hammerhead Ribozymes containing 2′-C-methyluridine:: a new RNA mimic [J].
Gallo, M ;
Far, RKK ;
Sczakiel, G ;
Iribarren, AM .
CHEMISTRY & BIODIVERSITY, 2005, 2 (02) :198-204
[6]   2′-C-methyluridine phosphoramidite:: a new building block for the preparation of RNA analogues carrying the 2′-hydroxyl group [J].
Gallo, M ;
Monteagudo, E ;
Cicero, DO ;
Torres, HN ;
Iribarren, AM .
TETRAHEDRON, 2001, 57 (27) :5707-5713
[7]  
GALLO M, 2002, THESIS U BUENOS AIRE
[8]   A short, flexible route toward 2'-C-branched ribonucleosides [J].
HarryOkuru, RE ;
Smith, JM ;
Wolfe, MS .
JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (06) :1754-1759
[9]   BRANCHED-CHAIN SUGAR NUCLEOSIDES .4. 2'-C-METHYLADENOSINE [J].
JENKINS, SR ;
ARISON, B ;
WALTON, E .
JOURNAL OF ORGANIC CHEMISTRY, 1968, 33 (06) :2490-&
[10]   Perspectives on chemistry and therapeutic applications of Locked Nucleic Acid (LNA) [J].
Kaur, Harleen ;
Babu, B. Ravindra ;
Maiti, Souvik .
CHEMICAL REVIEWS, 2007, 107 (11) :4672-4697