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Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and
David C Ireland1, Michelle L Colgrave, David J Craik
1Institute for Molecular Bioscience and Australian Research Council Special Research Centre for Functional and Applied Genomics, The University of Queensland, Brisbane QLD 4072, Australia.
The Biochemical Journal
|July 29, 2006
Summary
Cyclotides from Viola odorata exhibit remarkable stability and diverse bioactivities. These plant defense peptides, featuring a cyclic cystine knot (CCK) motif, show consistent resistance to enzymes, highlighting their potential as natural templates.
Area of Science:
- Biochemistry
- Plant Science
- Peptide Chemistry
Background:
- Cyclotides are plant-derived peptides with a unique head-to-tail cyclized backbone and cyclic cystine knot (CCK) structure.
- This CCK motif confers exceptional resistance to degradation, suggesting a role in plant defense against pests and pathogens.
Purpose of the Study:
- To investigate the cyclotide content and diversity in the sweet violet, Viola odorata.
- To characterize novel cyclotide sequences and assess their bioactivity and proteolytic stability.
Main Methods:
- Identification and sequencing of cyclotides from Viola odorata aerial parts and roots.
- Assay of hemolytic activity as a marker for bioactivity.
- Testing resistance to proteolysis using enzymes like trypsin, pepsin, and thermolysin.
- Structural determination of a novel cyclotide, cycloviolacin O14.
Main Results:
- Thirty cyclotides were identified, including 13 novel sequences, expanding knowledge of cyclotide natural diversity.
- New cyclotides demonstrated varying hemolytic activities, indicating sequence-dependent bioactivity.
- All tested cyclotides showed complete resistance to enzymatic degradation, confirming the inherent stability of the CCK framework.
- The CCK motif was confirmed in the structure of cycloviolacin O14.
Conclusions:
- Viola odorata is a rich source of diverse cyclotides with potential roles in plant defense.
- Cyclotide sequences influence bioactivity, but proteolytic stability is an intrinsic property of the CCK framework.
- Cyclotides represent a versatile natural template for developing new bioactive peptides for various applications.
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