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Updated: Dec 25, 2025
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
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Circular Permutation of the Native Enzyme-Mediated Cyclization Position in Cyclotides
Bronwyn J Smithies1, Yen-Hua Huang1, Mark A Jackson1
1Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
ACS Chemical Biology
|March 24, 2020
Summary
Researchers redesigned a cyclotide scaffold for easier, eco-friendly production. This new scaffold enables enzyme-mediated cyclization of engineered cyclotides, paving the way for large-scale pharmaceutical applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmaceutical Science
Background:
- Cyclotides are stable, cell-penetrating cyclic peptides used as pharmaceutical scaffolds.
- Current synthetic production methods raise cost and environmental concerns.
- Enzyme-mediated cyclization using Asparaginyl endopeptidases (AEPs) offers a sustainable alternative.
Purpose of the Study:
- To redesign the MCoTI-II cyclotide scaffold for improved AEP-mediated cyclization compatibility.
- To enable the incorporation of bioactive sequences in flexible regions without compromising cyclization.
- To facilitate large-scale production of engineered cyclotides.
Main Methods:
- Redesigning the MCoTI-II cyclotide scaffold to relocate the AEP cyclization site.
- Incorporating a bioactive peptide sequence into the modified scaffold.
- Demonstrating successful AEP-mediated cyclization of the engineered scaffold.
Main Results:
- A novel MCoTI-II scaffold compatible with AEP-mediated cyclization was successfully engineered.
- Bioactive peptide sequences were incorporated into the flexible region while maintaining cyclization efficiency.
- The redesigned scaffold overcomes previous limitations where bioactive insertions interfered with cyclization.
Conclusions:
- The engineered AEP-compatible cyclotide scaffold facilitates enzyme-mediated production.
- This approach enables the design of bioactive cyclotides compatible with sustainable production methods.
- The findings open possibilities for large-scale, eco-friendly production of cyclotides for pharmaceutical use.
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