Highly Efficient Cyclization Approach of Propargylated Peptides via Gold(I)-Mediated Sequential C-N, C-O, and C-C Bond Formation

Rajeshwer Vanjari, Emad Eid, Ganga B. Vamisetti, Shaswati Mandal, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

A rapid and efficient cyclization of unprotected N-propargylated peptides using the Au(I) organometallic complex is reported. The method relies on the activation of the propargyl functionality using gold(I) to produce a new linkage with the N-Terminus amine at the cyclization site. The presented method features a fast reaction rate (within 20 min), mild conditions, chemoselectivity, wide sequence scope, and high yields (up to 87%). The strategy was successfully tested on a wide variety of 30 unprotected peptides having various sequences and lengths, thus providing access to structurally distinct cyclic peptides. The practical usefulness of this method was demonstrated in producing peptides that bind efficiently to Lys48-linked di-And tetra-ubiquitin chains. The new cyclic peptide modulators exhibited high permeability to living cells and promoted apoptosis via binding with the endogenous Lys48-linked ubiquitin chains.

Original languageEnglish
Pages (from-to)2021-2028
Number of pages8
JournalACS Central Science
Volume7
Issue number12
DOIs
StatePublished - 22 Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry (all)
  • Chemical Engineering (all)

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