Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 62, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202215049
Keywords
Cyanovinylene; Excimer; Fluorescent Probes; G-Quadruplex; Self-Assembly
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In this study, a fluorogenic probe CV2 was developed for the selective monitoring of G-quadruplex (G4) structures in living cells. CV2 specifically recognizes parallel G4 DNA and forms self-assembled nanoaggregates with red excimer-emitting fluorescence. The specific binding of CV2 to G4s triggers its disassembly into monomeric dyes, leading to a significant fluorescence enhancement. Moreover, CV2 can selectively stain G4s in mitochondria, making it useful for investigating the potential roles of mitochondrial DNA G4s in diseases involving mitochondrial dysfunction.
The selective monitoring of G-quadruplex (G4) structures in living cells is important to elucidate their functions and reveal their value as diagnostic or therapeutic targets. Here we report a fluorogenic probe (CV2) able to selectively light-up parallel G4 DNA over antiparallel topologies. CV2 was constructed by conjugating the excimer-forming CV dye with a peptide sequence (l-Arg-l-Gly-glutaric acid) that specifically recognizes G4s. CV2 forms self-assembled, red excimer-emitting nanoaggregates in aqueous media, but specific binding to G4s triggers its disassembly into rigidified monomeric dyes, leading to a dramatic fluorescence enhancement. Moreover, selective permeation of CV2 stains G4s in mitochondria over the nucleus. CV2 was employed for tracking the folding and unfolding of G4s in living cells, and for monitoring mitochondrial DNA (mtDNA) damage. These properties make CV2 appealing to investigate the possible roles of mtDNA G4s in diseases that involve mitochondrial dysfunction.
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