Decoration of Coiled-Coil Peptides with N-Cysteine Peptide Thioesters As Cyclic Peptide Precursors Using Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) Click Reaction

Org Lett. 2018 Dec 7;20(23):7493-7497. doi: 10.1021/acs.orglett.8b03261. Epub 2018 Nov 8.


The development of a copper-catalyzed azide-alkyne cycloaddition (CuAAC) protocol for the decoration of coiled coils with N-cysteine peptide thioesters as cyclic peptide precursors is presented. The reaction conditions include tert-butanol/PBS as the solvent and CuSO4/THPTA/ascorbate as the catalytic system. During these studies, partial formylation of N-terminal cysteine peptides is observed. Mechanistic analysis leads to identification of the formyl source and, hence, to the development of reaction conditions, under which the undesired side reaction was suppressed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemistry*
  • Catalysis
  • Click Chemistry
  • Copper / chemistry*
  • Cycloaddition Reaction
  • Esters / chemistry*
  • Molecular Conformation
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Sulfhydryl Compounds / chemistry*


  • Alkynes
  • Azides
  • Esters
  • Peptides
  • Sulfhydryl Compounds
  • Copper