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タイトル: | Selective alkylation of T–T mismatched DNA using vinyldiaminotriazine–acridine conjugate |
著者: | Onizuka, Kazumitsu Usami, Akira Yamaoki, Yudai https://orcid.org/0000-0002-8927-4985 (unconfirmed) Kobayashi, Tomohito Hazemi, Madoka E Chikuni, Tomoko Sato, Norihiro Sasaki, Kaname Katahira, Masato https://orcid.org/0000-0003-0336-7660 (unconfirmed) Nagatsugi, Fumi |
著者名の別形: | 山置, 佑大 片平, 正人 |
発行日: | 16-Feb-2018 |
出版者: | Oxford University Press (OUP) |
誌名: | Nucleic Acids Research |
巻: | 46 |
号: | 3 |
開始ページ: | 1059 |
終了ページ: | 1068 |
抄録: | 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. |
著作権等: | © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
URI: | http://hdl.handle.net/2433/231100 |
DOI(出版社版): | 10.1093/nar/gkx1278 |
PubMed ID: | 29309639 |
出現コレクション: | 学術雑誌掲載論文等 |
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