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In Vivo Incorporation of Azide Groups into DNA by Using Membrane-Permeable Nucleotide Triesters.
Journal article

In Vivo Incorporation of Azide Groups into DNA by Using Membrane-Permeable Nucleotide Triesters.

  • Tera M Department of Chemistry, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
  • Glasauer SMK Department of Chemistry, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
  • Luedtke NW Department of Chemistry, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland.
  • 2018-06-29
Published in:
  • Chembiochem : a European journal of chemical biology. - 2018
DNA
chemical biology
click chemistry
metabolic labeling
nucleosides
nucleotides
Animals
Azides
Cell Membrane Permeability
Click Chemistry
DNA
Esters
HeLa Cells
Humans
Nucleotides
Zebrafish
Zidovudine
English Metabolic incorporation of bioorthogonal functional groups into cellular nucleic acids can be impeded by insufficient phosphorylation of nucleosides. Previous studies found that 5azidomethyl-2'-deoxyuridine (AmdU) was incorporated into the DNA of HeLa cells expressing a low-fidelity thymidine kinase, but not by wild-type HeLa cells. Here we report that membrane-permeable phosphotriester derivatives of AmdU can exhibit enhanced incorporation into the DNA of wild-type cells and animals. AmdU monophosphate derivatives bearing either 5'-bispivaloyloxymethyl (POM), 5'-bis-(4-acetoxybenzyl) (AB), or "Protide" protective groups were used to mask the phosphate group of AmdU prior to its entry into cells. The POM derivative "POM-AmdU" exhibited better chemical stability, greater metabolic incorporation efficiency, and lower toxicity than "AB-AmdU". Remarkably, the addition of POM-AmdU to the water of zebrafish larvae enabled the biosynthesis of azide-modified DNA throughout the body.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/215499
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