A new strategy for site-specific alkylation of DNA using oligonucleotides containing an abasic site and alkylating probes

Sato, Norihiro; Tsuji, Genichiro; Sasaki, Yoshihiro; Usami, Akira; Moki, Takuma; Onizuka, Kazumitsu; Yamada, Ken; Nagatsugi, Fumi

doi:10.1039/c5cc03915k

Cited by 17 publications

(10 citation statements)

References 30 publications

(45 reference statements)

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“…In our previous study, we developed 2-amino-6-vinylpurine (AVP) as a reactive moiety for the selective alkylation of the target thymine base ( 14 ). The AVP moiety was conjugated with Hoechst 33258 (Figure 1A ), and the selective alkylation of the thymine base opposite an amino purine (AP) site was achieved by a proximity effect.…”

Section: Introductionmentioning

confidence: 99%

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

Onizuka

Usami

Yamaoki

et al. 2018

Nucleic Acids Research

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The alkylation of the specific higher-order nucleic acid structures is of great significance in order to control its function and gene expression. In this report, we have described the T–T mismatch selective alkylation with a vinyldiaminotriazine (VDAT)–acridine conjugate. The alkylation selectively proceeded at the N3 position of thymidine on the T–T mismatch. Interestingly, the alkylated thymidine induced base flipping of the complementary base in the duplex. In a model experiment for the alkylation of the CTG repeats DNA which causes myotonic dystrophy type 1 (DM1), the observed reaction rate for one alkylation increased in proportion to the number of T–T mismatches. In addition, we showed that primer extension reactions with DNA polymerase and transcription with RNA polymerase were stopped by the alkylation. The alkylation of the repeat DNA will efficiently work for the inhibition of replication and transcription reactions. These functions of the VDAT–acridine conjugate would be useful as a new biochemical tool for the study of CTG repeats and may provide a new strategy for the molecular therapy of DM1.

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Section: Introductionmentioning

confidence: 99%

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

Onizuka

Usami

Yamaoki

et al. 2018

Nucleic Acids Research

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“…Knowing the potential of the VQ-precursor as a promising alkylating moiety, we were encouraged to utilize the compound to target other higher-ordered structures of nucleic acids such as an AP-site and T-T/U-U mismatch on DNA or RNA (Figure 9A). We have previously developed several 2-amino-6-vinylpurine (AVP)-conjugated ligands for the AP-site-targeting alkylation (34). The AP site allows a variety of ligands to recognize the site through hydrogen bonding in the generated hydrophobic pocket (35–41).…”

Section: Resultsmentioning

confidence: 99%

Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids

Onizuka

Hazemi

Sato

et al. 2019

Nucleic Acids Research

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Higher-ordered structure motifs of nucleic acids, such as the G-quadruplex (G-4), mismatched and bulge structures, are significant research targets because these structures are involved in genetic control and diseases. Selective alkylation of these higher-order structures is challenging due to the chemical instability of the alkylating agent and side-reactions with the single- or double-strand DNA and RNA. We now report the reactive OFF-ON type alkylating agents, vinyl-quinazolinone (VQ) precursors with a sulfoxide, thiophenyl or thiomethyl group for the OFF-ON control of the vinyl reactivity. The stable VQ precursors conjugated with aminoacridine, which bind to the G-4 DNA, selectively reacted with a T base on the G-4 DNA in contrast to the single- and double-strand DNA. Additionally, the VQ precursor reacted with the T or U base in the AP-site, G-4 RNA and T-T mismatch structures. These VQ precursors would be a new candidate for the T or U specific alkylation in the higher-ordered structures of nucleic acids.

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“…This vinyl chemistry can also be applied to develop reactive small molecules, and we have reported several compounds. [20][21][22][23][24][25][26] The vinyl derivative-containing oligonucleotides were developed to control gene expression by crosslinking formation. For creating a functional crosslinking structure, we used vinyl chemistry to synthesize crosslinked RNA 27 and 2′-OMe RNA duplexes.…”

Section: Creation Of Interstrand Crosslinking Structuresmentioning

confidence: 99%

Hybridization-specific chemical reactions to create interstrand crosslinking and threaded structures of nucleic acids

et al. 2022

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A new strategy for site-specific alkylation of DNA using oligonucleotides containing an abasic site and alkylating probes

Cited by 17 publications

References 30 publications

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate

Reactive OFF-ON type alkylating agents for higher-ordered structures of nucleic acids

Hybridization-specific chemical reactions to create interstrand crosslinking and threaded structures of nucleic acids

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