The interstrand crosslinking of nucleic acids is one of the strategies to create the stable complex between an oligonucleotide and RNA by covalent bond formation. We previously reported that fully 2'-O-methylated (2'-OMe) RNAs having the 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. In this study, we established a chemical method to efficiently synthesize the crosslinked 2'-OMe RNA duplexes using AVP and prepared the anti-miRNA oligonucleotides (AMOs) containing the antisense targeting miR-21 and crosslinked duplex at the terminal sequences. These AMOs showed a markedly higher anti miRNA activity than that of the commercially-available miR-21 inhibitor which has locked nucleic acid (LNA) residues.
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Synthesis of Crosslinked 2'-OMe RNA Duplexes Using 2-Amino-6-Vinylpurine and Their Application for Effective Inhibition of miRNA Function.
Curr Protoc
March 2022
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai, Miyagi, Japan.
Crosslinking reactions to nucleic acids are an effective way to prepare stable complexes formed by covalent bonding. We demonstrated that fully 2'-O-methylated (2'-OMe) RNAs having a 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. Recently, we reported the preparation of crosslinked 2'-OMe RNA duplexes using AVP and the anti-miRNA oligonucleotides (AMOs) containing crosslinked duplexes at the terminal positions.
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Biotechnol J
February 2022
Department of Immunology and Theranostics, City of Hope, Duarte, California, USA.
Background: Genetic engineered Bispecific T-cell engagers (BiTEs) generate potent cytotoxic effects.
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Synthesis of crosslinked 2'-OMe RNA duplexes and their application for effective inhibition of miRNA function.
Bioorg Med Chem Lett
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Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan. Electronic address:
The interstrand crosslinking of nucleic acids is one of the strategies to create the stable complex between an oligonucleotide and RNA by covalent bond formation. We previously reported that fully 2'-O-methylated (2'-OMe) RNAs having the 2-amino-6-vinylpurine (AVP) exhibited an efficient crosslinking to uracil in the target RNA. In this study, we established a chemical method to efficiently synthesize the crosslinked 2'-OMe RNA duplexes using AVP and prepared the anti-miRNA oligonucleotides (AMOs) containing the antisense targeting miR-21 and crosslinked duplex at the terminal sequences.
View Article and Find Full Text PDFPhotoinduced DNA Interstrand Cross-Linking by Benzene Derivatives: Leaving Groups Determine the Efficiency of the Cross-Linker.
J Org Chem
January 2021
Department of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin Milwaukee, 3210 N. Cramer Street, Milwaukee, Wisconsin 53211, United States.
We have synthesized and characterized two small libraries of 2-OMe or 2-NO-benzene analogues - and - containing a wide variety of leaving groups. Irradiation of these compounds at 350 nm generated benzyl radicals that were spontaneously oxidized to benzyl cations directly producing DNA interstrand cross-links (ICLs). Compounds with a 2-methoxy substituent showed a faster cross-linking reaction rate and higher ICL efficiency than the corresponding 2-nitro analogues.
View Article and Find Full Text PDFSynthesis of RNA Crosslinking Oligonucleotides Modified with 2-Amino-7-Deaza-7-Propynyl-6-Vinylpurine.
Curr Protoc Nucleic Acid Chem
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Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai-shi, Japan.
This article describes procedures to synthesize 2'-OMe-RNA modified with cross-linkable 2-amino-7-deaza-7-propynyl-6-vinylpurine (ADpVP) and preparation of the RNA-crosslinking experiment in vitro. All synthesis steps yield the desired compound in moderate or high yield without expensive chemical reagents or specific devices. The crosslink-active form of modified RNA can also be purified by commonly used reversed-phase HPLC, can be stored at -80°C after lyophilization for a few days, and is ready to use for crosslinking experiments.
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