論文

査読有り 国際誌
2020年10月8日

Target identification of a macrocyclic hexaoxazole G-quadruplex ligand using post-target-binding visualization.

Chemical communications (Cambridge, England)
  • Mizuho Yasuda
  • ,
  • Yue Ma
  • ,
  • Sachiko Okabe
  • ,
  • Yuki Wakabayashi
  • ,
  • Dongdong Su
  • ,
  • Young-Tae Chang
  • ,
  • Hiroyuki Seimiya
  • ,
  • Masayuki Tera
  • ,
  • Kazuo Nagasawa

56
85
開始ページ
12905
終了ページ
12908
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1039/d0cc04957c

Macrocyclic hexaoxazoles (6OTDs) are G-quadruplex (G4) ligands, and some derivatives, such as L2H2-6OTD (1a) bearing two aminobutyl side chains, show cytotoxicity towards cancer cells. To identify the cellular target of 1a, we employed a post-target-binding strategy utilizing click reaction (Huisgen cyclization) between the azide-conjugated ligand L2H2-6OTD-Az (1b) and the cell-permeable dye CO-1 bearing a strained alkyne moiety and the BODIPY fluorophore under Cu-free conditions. We confirmed that introduction of the small azide group did not alter the physical or biological properties, including anti-cancer activity, of 1a, and we also demonstrated bias-free localization of CO-1. The post-binding visualization strategy suggested that L2H2-6OTD (1a) colocalized with RNA G4 in living cells.

リンク情報
DOI
https://doi.org/10.1039/d0cc04957c
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33030187
ID情報
  • DOI : 10.1039/d0cc04957c
  • PubMed ID : 33030187

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