Manipulating the Click Reactivity of Dibenzoazacyclooctynes: From Azide Click Component to Caged Acylation Reagent by Silver Catalysis

Angew Chem Int Ed Engl. 2020 Nov 2;59(45):19940-19944. doi: 10.1002/anie.202009408. Epub 2020 Aug 31.

Abstract

Strain-promoted azide-alkyne cycloaddition using dibenzoazacyclooctyne (DBCO) is widely applied in copper-free bioorthogonal reactions. Reported here is the efficient acid-promoted rearrangement and silver-catalyzed amidation of DBCO, which alters its click reactivity robustly. In the switched click reaction, DBCO, as a caged acylation reagent, enables rapid peptide/protein modification after decaging facilitated by silver catalysts, rendering site-specific conjugation of an IgG antibody by a Fc-targeting peptide.

Keywords: acylation; click chemistry; peptides; rearrangements; silver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Alkynes / chemistry*
  • Azides / chemistry*
  • Catalysis
  • Click Chemistry*
  • Indicators and Reagents / chemistry
  • Silver / chemistry*
  • Spectrum Analysis / methods

Substances

  • Alkynes
  • Azides
  • Indicators and Reagents
  • Silver