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The circular protein backbone and knotted arrangement of
disulfide bonds makes the cyclotides exceptionally stable. In
their native medicine uses, for example, the peptides are boiled
when the plant Oldenlandia affinis is used to make a tea that
women ingest to accelerate childbirth. The peptides are
exceptionally stable to enzymatic degradation. Because of this
stability, they represent useful templates in pharmaceutical
applications.
A recent review (Craik, et al., 2002) summarises
some of these applications.
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Strategy for the utilisation of cyclotides in drug
design. |
The cyclotides appear to act as defence molecules in plants
(Jennings, et al., 2001) as they have potent
insecticidal activity. The figure below shows their marked
effects on growth and development of Helicoverpa species
fed a diet containing cyclotides (small insects) relative to
controls (large insects).
The potential exists to make transgenic plants containing genes
for the protection of crop plants from insect pests.
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The results of a kalata B1 diet on Helicoverpa
species. Small larvae were fed a diet containing kalata B1, the
large larvae were fed a normal diet. |
References
Craik D J, Simonsen S, Daly N L: The cyclotides: Novel
macrocyclic peptides as scaffolds in drug design. Current Opinion
in Drug Discovery & Development (2002, in press).
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.
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