Uses of Cyclotides

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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.

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.

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.