[1] Typically containing 28-37 amino acids, they are characterized by their head-to-tail cyclised peptide backbone and the interlocking arrangement of their three disulfide bonds.

[2][3][4] Cyclotides have a well-defined three-dimensional structure due to their interlocking disulfide bonds and cyclic peptide backbone.

[11] Analysis of the suite of known cyclotides reveals many sequence similarities that are important for understanding their unique physico-chemical properties, bioactivities and homology.

Although the cysteines appear essential to maintaining the overall fold, several other residues highly conserved in cyclotides are thought to provide additional stability.

[6] The generic configuration of the precursor protein consists of an endoplasmic reticulum signal sequence, a non-conserved pro-region, a highly conserved region known as the N-terminal repeat (NTR), the mature cyclotide domain and finally a short hydrophobic C-terminal tail.

[17] Recently, the enzyme responsible for the backbone cyclization of cyclotides has been isolated from the medicinal plant Clitoria ternatea.

[19] Interest in these has recently intensified with the publications of a chemical methodology capable of synthetically producing cyclotides with high yields,[20][21] and the amenability of the CCK framework to amino-acid substitutions.

[22] But for molecules to be useful in a therapeutic setting they require useful biopharmaceutical characteristics such as resistance to proteolysis and membrane permeability.

[24] Furthermore, enzymatic digestion of cystine knot peptide drugs was associated with only a few proteases and it was suggested that this limitation may be overcome by mutating out particular cleavage sites.

[25][26] During a Red Cross relief mission in the Democratic Republic of Congo during the 1960s, a Norwegian doctor, Lorents Gran, noted that during labor some African women used a medicinal tea made from the leaves of the plant Oldenlandia affinis to induce labor and facilitate childbirth.