A Kinetic and Fluorogenic Enhancement Strategy for Labeling of Nucleic Acids.
Angew Chem Int Ed Engl
; 61(22): e202112931, 2022 05 23.
Article
em En
| MEDLINE
| ID: mdl-35139255
ABSTRACT
Chemical modification of nucleic acids in living cells can be sterically hindered by tight packing of bioorthogonal functional groups in chromatin. To address this limitation, we report here a dual enhancement strategy for nucleic acid-templated reactions utilizing a fluorogenic intercalating agent capable of undergoing inverse electron-demand Diels-Alder (IEDDA) reactions with DNA containing 5-vinyl-2'-deoxyuridine (VdU) or RNA containing 5-vinyl-uridine (VU). Reversible high-affinity intercalation of a novel acridine-tetrazine conjugate "PINK" (KD =5±1â
µM) increases the reaction rate of tetrazine-alkene IEDDA on duplex DNA by 60 000-fold (590â
M-1 s-1 ) as compared to the non-templated reaction. At the same time, loss of tetrazine-acridine fluorescence quenching renders the reaction highly fluorogenic and detectable under no-wash conditions. This strategy enables live-cell dynamic imaging of acridine-modified nucleic acids in dividing cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Nucleicos
/
Compostos Heterocíclicos
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2022
Tipo de documento:
Article