Target identification of a macrocyclic hexaoxazole G-quadruplex ligand using post-target-binding visualization.
Chem Commun (Camb)
; 56(85): 12905-12908, 2020 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-33030187
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
/
Compostos Macrocíclicos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article