Development of Near-Infrared Nucleic Acid Mimics of Fluorescent Proteins for In Vivo Imaging of Viral RNA with Turn-On Fluorescence.
J Am Chem Soc
; 143(46): 19317-19329, 2021 11 24.
Article
em En
| MEDLINE
| ID: mdl-34762804
ABSTRACT
GFP-like fluorescent proteins and their molecular mimics have revolutionized bioimaging research, but their emissions are largely limited in the visible to far-red region, hampering the in vivo applications in intact animals. Herein, we structurally modulate GFP-like chromophores using a donor-acceptor-acceptor (D-A-A') molecular configuration to discover a set of novel fluorogenic derivatives with infrared-shifted spectra. These chromophores can be fluorescently elicited by their specific interaction with G-quadruplex (G4), a unique noncanonical nucleic acid secondary structure, via inhibition of the chromophores' twisted-intramolecular charge transfer. This feature allows us to create, for the first time, FP mimics with tunable emission in the near-infrared (NIR) region (Emmax = 664-705 nm), namely, infrared G-quadruplex mimics of FPs (igMFP). Compared with their FP counterparts, igMFPs exhibit remarkably higher quantum yields, larger Stokes shift, and better photostability. In a proof-of-concept application using pathogen-related G4s as the target, we exploited igMFPs to directly visualize native hepatitis C virus (HCV) RNA genome in living cells via their in situ formation by the chromophore-bound viral G4 structure in the HCV core gene. Furthermore, igMFPs are capable of high contrast HCV RNA imaging in living mice bearing a HCV RNA-presenting mini-organ, providing the first application of FP mimics in whole-animal imaging.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Viral
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Ácidos Nucleicos
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Fluorescência
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Corantes Fluorescentes
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Proteínas Luminescentes
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article