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.
H. armigera - the three large caterpillars were
not fed kalata B1, the small ones were. |
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
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)
Gran L: Isolation of oxytocic peptides from Oldenlandia affinis by
solvent extraction of tetraphenylborate complexes and
chromatography on sephadex LH-20. Lloydia (1973a)
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)
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)
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.