Target identification of a macrocyclic hexaoxazole G-quadruplex ligand using post-target-binding visualization. Issue 85 (8th October 2020)

• Record Type: Journal Article
• Authors: Yasuda, Mizuho; Ma, Yue; Okabe, Sachiko; Wakabayashi, Yuki; Su, Dongdong; Chang, Young-Tae; Seimiya, Hiroyuki; Tera, Masayuki; Nagasawa, Kazuo
• Is Part Of: Chemical communications. Volume 56:Issue 85(2020)
• Page Start: 12905
• Page End: 12908
• Publication Date: 2020-10-08
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc04957c
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Macrocyclic hexaoxazoles (6OTD) are G-quadruplex (G4) ligands. The azide-modified derivative L2H2-6OTD-Az shows cytotoxicity towards cancer cells and visualizes G4 in live cells together with BODIPY bearing a strained-alkyne (CO-1). Abstract : 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.