Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides

Angel Santorelli, Kurt V. Gothelf*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Labelling of oligonucleotides with dyes, targeting ligands, and other moieties has become ever more essential in life-sciences. Conventionally, modifications are introduced to oligonucleotides during solid phase synthesis by special phosphoramidites functionalised with a chemical handle or the desired functional group. In this work, we present a facile and inexpensive method to introduce modifications to oligonucleotides without the need for special phosphoramidites. Sulfonyl azides are applied to react with one or more selected phosphite intermediates during solid phase synthesis. We have prepared 11 sulfonyl azides with different chemical handles such as amine, azide, alkyne, and thiol, and we have further introduced functionalities such as pyrene, other dyes, photo-switchable azobenzenes, and a steroid. The method is compatible with current phosphoramidite-based automated oligonucleotide synthesis and serves as a simple alternative to the unstable and expensive special phosphoramidites currently used for conjugation to oligonucleotides.

Original languageEnglish
JournalNucleic Acids Research
Volume50
Issue13
Pages (from-to)7235-7246
Number of pages12
ISSN0305-1048
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Azides
  • Coloring Agents
  • DNA
  • Oligonucleotides
  • Solid-Phase Synthesis Techniques

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