Biological Activity

What are Cyclotides?
Uses of Cyclotides
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Discovery of Cyclotides
Biological Activity
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Cyclotide Genes
Cystine Knots
Other Circular Proteins
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H. armigera on tomato, one of the crops targeted by this pest insect.
H. armigera adult

H. armigera - the three large caterpillars were not fed kalata B1, the small ones were.
Cyclotides have a diverse range of biological activities including uterotonic activity (Gran, 1973a) Anti-HIV (Gustafson, et al., 1994), neurotensin inhibition (Witherup, et al., 1994), antimicrobial (Tam, et al., 1999b) and insecticidal activity.

The mechanisms of actions of the various activities are very poorly understood. It is believed that anti-bacterial activities may result from membrane disruption by the hydrophobic cyclotides. How the cyclotides mediate biological activity in humans, activities such as neurotensin inhibition and uterotonicity, is not known although it is not impossible that some type of receptor mediated processes are at work.

Feeding trials have been conducted on the larvae of Helicoverpa punctigera, a pest moth that affects commercial crops in Australia and other countries (see side panel), that showed kalata B1 inhibited the growth of these larvae, preventing development beyond the first instar stage (Jennings, et al., 2001). It was also shown that kalata B1 was a powerful deterent with food laced with kalata B1 ignored by the larvae. Whether this is the primary biological activity of the cyclotides in plants is not known.

The structure of kalata B1 crawling with H. punctigera larvae. The opposite of what would happen in reality as these larvae seem to be repulsed by the cyclotides.


Craik DJ, Daly NL, Bond T and Waine C: Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J. Mol. Biol. (1999) 294:1327-1336.

Gran L: Isolation of oxytocic peptides from Oldenlandia affinis by solvent extraction of tetraphenylborate complexes and chromatography on sephadex LH-20. Lloydia (1973a) 36:207-208.

Gustafson KR, Sowder II RC, Henderson LE, Parsons IC, Kashman Y, Cardellina II JH, McMahon JB, Buckheit Jr. RW, Pannell LK and Boyd MR: Circulins A and B: Novel HIV-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia. J. Am. Chem. Soc. (1994) 116:9337-9338.

Jennings C, West J, Waine C, Craik D, Anderson M: Biosynthesis and insecticidal properties of plant cyclotides - the cyclic knotted proteins from O. affinis. PNAS (2001) 98, 10614-10619.

Tam JP, Lu YA, Yang JL and Chiu KW: An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides.Proc. Natl. Acad. Sci. U S A (1999b) 96:8913-8918.

Witherup KM, Bogusky MJ, Anderson PS, Ramjit H, Ransom RW, Wood T and Sardana M: Cyclopsychotride A, A biologically active, 31-residue cyclic peptide isolated from Psychotria Longipes. J. Nat. Prod. (1994) 57:1619-1625.