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Updated: Nov 7, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Semisynthetic head-to-tail cyclized peptides obtained by combining protein trans-splicing and intramolecular
Shubhendu Palei1, Henning D Mootz1
1Institute of Biochemistry, University of Muenster, Münster 48149, Germany. henning.mootz@uni-muenster.de and International Graduate School of Chemistry (GSC-MS), University of Muenster, Münster 48149, Germany.
Abstract:
A dual-intein approach for the preparation of head-to-tail macrocyclic peptides is reported, where synthetic and genetically encoded fragments are ligated by two native peptide bonds. A split intein ligates the synthetic and genetically encoded peptides via protein trans-splicing and is followed by intramolecular cyclization through an expressed protein ligation step mediated with a cis-intein. We identified a suitable pair of orthogonal inteins and optimized the conditions for a one-pot cyclization protocol. We report the semisynthesis of model macrocyles with various ring sizes and of the natural product sunflower trypsin inhibitor (SFTI) along with its ornithine analog.
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