The chemistry and biology of cyclotides

Cyclotides are mini-proteins with a macrocyclic peptide backbone and cystine-knot arrangement of disulfide bonds that makes them exceptionally stable to chemical, thermal or enzymatic degradation. They have a diverse range of bioactivities and are amenable to chemical synthesis, making them accessible as molecular templates for protein engineering and drug design applications. In the last two years, methods have been developed for the production of cyclotides using inteins in bacterial expression systems and using plant cell cultures, adding to established methods based on solid-phase peptide synthesis. The availability of an enhanced armory of synthetic methods promises to expand the potential range of cyclotide-based applications.