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Updated: May 23, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

Cyclotides as a basis for drug design.

David J Craik¹, Joakim E Swedberg, Joshua S Mylne

¹The University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia. d.craik@imb.uq.edu.au

Expert Opinion on Drug Discovery

|April 4, 2012

Summary

Cyclotides, stable cyclic peptides, show promise as drug leads and diagnostic agents due to their unique structure. Further research into synthetic cyclotides is needed for clinical trials.

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Area of Science:

Biochemistry
Medicinal Chemistry
Drug Discovery

Background:

Cyclotides are plant-derived cyclic peptides characterized by a head-to-tail cyclic backbone and a conserved six-cysteine knot.
They exhibit diverse biological activities, including uterotonic and anti-HIV effects, making them attractive for pharmaceutical development.
Their inherent stability and unique structure position cyclotides as valuable peptide-based scaffolds for drug design.

Purpose of the Study:

To review recent literature on the therapeutic applications of naturally occurring and synthetically modified cyclotides.
To explore the use of cyclotides and cyclotide-like molecules as peptide-based drug leads and diagnostic agents.

Main Methods:

Literature review of therapeutic applications of cyclotides.
Analysis of studies on naturally occurring and synthetically modified cyclotides.
Inclusion of applications as peptide-based drug leads and diagnostic agents.

Main Results:

Cyclotides are ultra-stable and serve as promising templates for drug development.
Bioactive peptide sequences can be successfully grafted onto cyclotide frameworks, maintaining biological activity.
Proof-of-concept studies demonstrate potential applications in cancer, cardiovascular diseases, and infectious diseases.

Conclusions:

Synthetic cyclotides require further investigation into biopharmaceutical properties and toxicities for human clinical trials.
Solid phase peptide synthesis is currently the primary method for producing modified cyclotides, with biological production methods showing progress.
Grafting bioactive sequences onto cyclotide scaffolds offers a stable platform for developing novel therapeutics.