A Kinetic and Fluorogenic Enhancement Strategy for Labeling of Nucleic Acids.

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 ± 1 μM) increases the reaction rate of tetrazine-alkene IEDDA on duplex DNA by 60,000-fold (590 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.

• Publication year

  2022

• Venue

  Angewandte Chemie

• Publication date

  2022-02-09

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1002/anie.202112931PMID 35139255
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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