Gold(I)-Mediated Rapid Cyclization of Propargylated Peptides via Imine Formation

Rajeshwer Vanjari, Deepanjan Panda, Shaswati Mandal, Ganga B. Vamisetti, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


In fundamental research and drug discovery, there is still a need for effective and straightforward chemical approaches for generating cyclic peptides. The divergent synthesis of cyclic peptides remains a challenge, in particular when cyclization is carried out in the presence of unprotected side chains and a nonpeptidic component within the cycle is needed. Herein, we describe a novel and efficient strategy based on Au(I)-mediated cyclization of unprotected peptides through rapid (30-60 min) amine addition on a propargyl group to generate an imine linkage. Mechanistic insights reveal that the reaction proceeds via regioselective Markovnikov's addition of the amine on the Au(I)-activated propargyl. This strategy was successfully applied to prepare efficiently (56-94%) over 35 diverse cyclic peptides having different sequences and lengths. We have also achieved stereoselective reduction of cyclic imines employing chiral ligands. The practicality of our method was extended for the synthesis of cyclic peptides that bind Lys48-linked di-ubiquitin chains with high affinity, leading to apoptosis of cancer cells.

Original languageEnglish
Pages (from-to)4966-4976
Number of pages11
JournalJournal of the American Chemical Society
Issue number11
StatePublished - 23 Mar 2022
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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