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

Kazumitsu Onizuka, Madoka E. Hazemi, Norihiro Sato, Gen Ichiro Tsuji, Shunya Ishikawa, Mamiko Ozawa, Kousuke Tanno, Ken Yamada, Fumi Nagatsugi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6578-6589
Number of pages12
JournalNucleic acids research
Volume47
Issue number13
DOIs
Publication statusPublished - 2019 Jul 26

ASJC Scopus subject areas

  • Genetics

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