Discovery of Cyclotides: A New Family of Ultra-Stable Circular Peptides From Plants | Research

The takeaway

Sixteen new cyclotides were discovered in plants, establishing a unique peptide family with exceptional stability from their circular backbone and knotted disulfide bonds, with potential antimicrobial and anti-HIV applications.

16 new peptides
Dramatically expanded the known cyclotide family, all sharing the ultra-stable cyclic cystine knot structure

What the researchers found

Sixteen novel cyclotides were identified from three plant species, all sharing the cyclic cystine knot motif that confers exceptional thermal, chemical, and enzymatic stability, with diverse bioactivities including antimicrobial and anti-HIV effects.

Why it matters

Cyclotides' extraordinary stability solves one of the biggest problems in peptide drug development — most peptides are quickly destroyed in the body. Their circular, knotted structure could serve as a template for designing stable oral peptide drugs.

How the study worked

In-vitro study using extraction, HPLC purification, mass spectrometry, and NMR structural characterization to identify and characterize cyclotides from Viola hederaceae, Viola odorata, and Oldenlandia affinis plant extracts.

What this study cannot tell us

Discovery and structural characterization study. Bioactivities described are primarily from initial screening. Detailed mechanism of action and therapeutic potential require further study.

How to read the evidence

Moderate evidence from a comprehensive discovery study with structural characterization and initial bioactivity screening of a novel peptide family.

When this study was published

Published in 1999. Cyclotide research has grown enormously since, with cyclotide drug scaffolds now in preclinical development for various diseases.

The bigger picture

Traditional peptide drugs break down quickly in the body. Cyclotides show that nature has already solved this stability problem. By grafting drug-like sequences into the cyclotide framework, researchers could create an entirely new class of stable oral peptide medicines.

Questions still open

Can cyclotides be used as drug scaffolds for oral peptide therapeutics?
What is the mechanism behind cyclotide anti-HIV activity?
Can cyclotides be produced economically by chemical synthesis or bioengineering?

Common questions

What makes cyclotides special?

Unlike most peptides that break down in minutes, cyclotides have a circular backbone with interlocking disulfide bonds that make them incredibly stable against heat, acid, and digestive enzymes — potentially enabling oral peptide drugs.

Could these become medicines?

Yes. Researchers are using cyclotides as stable scaffolds by inserting drug sequences into their framework. This could create oral peptide drugs for conditions currently requiring injections.

Read the original research

Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif.

Journal of molecular biology, 294(5), 1327-36

View on PubMed ↗

Citation

Craik, D J; Daly, N L; Bond, T; Waine, C. (1999). Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif.. Journal of molecular biology, 294(5), 1327-36.