Site-specific conjugation of drug-like fragments to an antimiR scaffold as a strategy to target miRNAs inside RISC

被引：9

作者：

Brunschweiger, A. ^{[1
]}

Gebert, L. F. R. ^{[1
]}

Lucic, M. ^{[1
]}

Pradere, U. ^{[1
]}

Jahns, H. ^{[1
]}

Berk, C. ^{[1
]}

Hunziker, J. ^{[2
]}

Hall, J. ^{[1
]}

机构：

[1] ETH, Dept Chem & Appl Biosci, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland

[2] Novartis Inst BioMed Res, Global Discovery Chem, CH-4056 Basel, Switzerland

来源：

CHEMICAL COMMUNICATIONS | 2016年 / 52卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

OLIGONUCLEOTIDES; MICRORNA; RECOGNITION; INHIBITORS; LIBRARY; RNAS; DNA;

D O I：

10.1039/c5cc07478a

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We synthesized a miR-122 antimiR library in which drug-like fragments were site-specifically introduced to short 20-O-methyl-RNAs. At some sites selected fragments elevated cellular antimiR activity to that of an unmodified 23mer antimiR, whereas at others the same fragments abolished activity. The potency of the antimiRs correlated with uptake into miRISC.

引用

页码：156 / 159

页数：4

共 23 条

[1] MicroRNAs: Target Recognition and Regulatory Functions [J].

Bartel, David P. .

CELL, 2009, 136 (02) :215-233

[2] Short, terminally modified 2′-OMe RNAs as inhibitors of microRNA [J].

Blechinger, Jenny ;

Pieper, Hanna ;

Marzenell, Paul ;

Kovbasyuk, Larisa ;

Serva, Andrius ;

Starkuviene, Vytaute ;

Erfle, Holger ;

Mokhir, Andriy .

CHEMICAL COMMUNICATIONS, 2013, 49 (67) :7397-7399

[3] Design and Implementation of an Ribonucleic Acid (RNA) Directed Fragment Library [J].

Bodoor, Khaled ;

Boyapati, Vamsi ;

Gopu, Vikram ;

Boisdore, Marietta ;

Allam, Kiran ;

Miller, Janae ;

Treleaven, W. Dale ;

Weldeghiorghis, Thomas ;

Aboul-ela, Fareed .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (12) :3753-3761

[4] Whole-body scanning PCR; a highly sensitive method to study the biodistribution of mRNAs, noncoding RNAs and therapeutic oligonucleotides [J].

Boos, Julien A. ;

Kirk, David W. ;

Piccolotto, Mari-Luz ;

Zuercher, Werner ;

Gfeller, Sandro ;

Neuner, Philippe ;

Dattler, Andre ;

Wishart, William L. ;

Von Arx, Fabian ;

Beverly, Michael ;

Christensen, Jesper ;

Litherland, Karine ;

van de Kerkhof, Esther ;

Swart, Pieter J. ;

Faller, Thomas ;

Beyerbach, Armin ;

Morrissey, David ;

Hunziker, Juerg ;

Beuvink, Iwan .

NUCLEIC ACIDS RESEARCH, 2013, 41 (15) :e145

[5] Target-induced selection of ligands from a dynamic combinatorial library of mono- and bi-conjugated oligonucleotides [J].

Bugaut, A ;

Bathany, K ;

Schmitter, JM ;

Rayner, B .

TETRAHEDRON LETTERS, 2005, 46 (04) :687-690

[6] Improved targeting of miRNA with antisense oligonucleotides [J].

Davis, Scott ;

Lollo, Bridget ;

Freier, Susan ;

Esau, Christine .

NUCLEIC ACIDS RESEARCH, 2006, 34 (08) :2294-2304

[7] Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing [J].

Deleavey, Glen F. ;

Damha, Masad J. .

CHEMISTRY & BIOLOGY, 2012, 19 (08) :937-954

[8] LNA-mediated microRNA silencing in non-human primates [J].

Elmen, Joacim ;

Lindow, Morten ;

Schutz, Sylvia ;

Lawrence, Matthew ;

Petri, Andreas ;

Obad, Susanna ;

Lindholm, Marie ;

Hedtjarn, Maj ;

Hansen, Henrik Frydenlund ;

Berger, Urs ;

Gullans, Steven ;

Kearney, Phil ;

Sarnow, Peter ;

Straarup, Ellen Marie ;

Kauppinen, Sakari .

NATURE, 2008, 452 (7189) :896-U10

[9] The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC [J].

Fabian, Marc R. ;

Sonenberg, Nahum .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (06) :586-593

[10] Miravirsen (SPC3649) can inhibit the biogenesis of miR-122 [J].

Gebert, Luca F. R. ;

Rebhan, Mario A. E. ;

Crivelli, Silvia E. M. ;

Denzler, Remy ;

Stoffel, Markus ;

Hall, Jonathan .

NUCLEIC ACIDS RESEARCH, 2014, 42 (01) :609-621

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