Synthesis and Properties of 2′-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives

Ken Yamada; Yusuke Abe; Hirotaka Murase; Yuta Ida; Shinya Hagihara; Fumi Nagatsugi

doi:10.1021/acs.joc.8b01002

Synthesis and Properties of 2′-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives

Ken Yamada, Yusuke Abe, Hirotaka Murase, Yuta Ida, Shinya Hagihara, Fumi Nagatsugi

Division of Organic- and Biomaterials Research

Research output: Contribution to journal › Article

3 Citations (Scopus)

Abstract

Cross-linkable 7-deaza-6-vinylguanosine (ADVP) and 7-propynyl-7-deaza-6-vinylguanosine (ADpVP) derivatives were synthesized and successfully incorporated into 2′-OMe-RNA oligonucleotides by solid-phase oligonucleotide synthesis. Analysis of their cross-link properties revealed that the 7-propynyl substituent on ADpVP induces a significant enhancement of the cross-link kinetics of the proximal 6-vinyl group to the complementary uracil base in the target RNA compared to that of ADVP. In addition, the 2′-OMe-RNA oligonucleotide containing ADpVP exhibited a higher antisense effect on luciferase production in the cell lysate than that of ADVP. These results suggested that the 7-substituted 7-deaza-6-vinylguanosine derivatives can be used as potent cross-linkers to target mRNA inside of cells.

Original language	English
Pages (from-to)	8851-8862
Number of pages	12
Journal	Journal of Organic Chemistry
Volume	83
Issue number	16
DOIs	https://doi.org/10.1021/acs.joc.8b01002
Publication status	Published - 2018 Aug 17

ASJC Scopus subject areas

Organic Chemistry

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Yamada, K., Abe, Y., Murase, H., Ida, Y., Hagihara, S., & Nagatsugi, F. (2018). Synthesis and Properties of 2′-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives. Journal of Organic Chemistry, 83(16), 8851-8862. https://doi.org/10.1021/acs.joc.8b01002

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title = "Synthesis and Properties of 2′-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives",

abstract = "Cross-linkable 7-deaza-6-vinylguanosine (ADVP) and 7-propynyl-7-deaza-6-vinylguanosine (ADpVP) derivatives were synthesized and successfully incorporated into 2′-OMe-RNA oligonucleotides by solid-phase oligonucleotide synthesis. Analysis of their cross-link properties revealed that the 7-propynyl substituent on ADpVP induces a significant enhancement of the cross-link kinetics of the proximal 6-vinyl group to the complementary uracil base in the target RNA compared to that of ADVP. In addition, the 2′-OMe-RNA oligonucleotide containing ADpVP exhibited a higher antisense effect on luciferase production in the cell lysate than that of ADVP. These results suggested that the 7-substituted 7-deaza-6-vinylguanosine derivatives can be used as potent cross-linkers to target mRNA inside of cells.",

author = "Ken Yamada and Yusuke Abe and Hirotaka Murase and Yuta Ida and Shinya Hagihara and Fumi Nagatsugi",

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T1 - Synthesis and Properties of 2′-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives

AU - Yamada, Ken

AU - Abe, Yusuke

AU - Murase, Hirotaka

AU - Ida, Yuta

AU - Hagihara, Shinya

AU - Nagatsugi, Fumi

PY - 2018/8/17

Y1 - 2018/8/17

N2 - Cross-linkable 7-deaza-6-vinylguanosine (ADVP) and 7-propynyl-7-deaza-6-vinylguanosine (ADpVP) derivatives were synthesized and successfully incorporated into 2′-OMe-RNA oligonucleotides by solid-phase oligonucleotide synthesis. Analysis of their cross-link properties revealed that the 7-propynyl substituent on ADpVP induces a significant enhancement of the cross-link kinetics of the proximal 6-vinyl group to the complementary uracil base in the target RNA compared to that of ADVP. In addition, the 2′-OMe-RNA oligonucleotide containing ADpVP exhibited a higher antisense effect on luciferase production in the cell lysate than that of ADVP. These results suggested that the 7-substituted 7-deaza-6-vinylguanosine derivatives can be used as potent cross-linkers to target mRNA inside of cells.

AB - Cross-linkable 7-deaza-6-vinylguanosine (ADVP) and 7-propynyl-7-deaza-6-vinylguanosine (ADpVP) derivatives were synthesized and successfully incorporated into 2′-OMe-RNA oligonucleotides by solid-phase oligonucleotide synthesis. Analysis of their cross-link properties revealed that the 7-propynyl substituent on ADpVP induces a significant enhancement of the cross-link kinetics of the proximal 6-vinyl group to the complementary uracil base in the target RNA compared to that of ADVP. In addition, the 2′-OMe-RNA oligonucleotide containing ADpVP exhibited a higher antisense effect on luciferase production in the cell lysate than that of ADVP. These results suggested that the 7-substituted 7-deaza-6-vinylguanosine derivatives can be used as potent cross-linkers to target mRNA inside of cells.

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