Cyclotide

[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.

It is convenient to discuss sequences in terms of the backbone segments, or loops, between successive cysteine residues.

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.

[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.

The stunting effect of kalata B1 cyclic peptide on growth and development of Helicoverpa punctigera , a caterpillar from the Lepidopteran order. [ 6 ]
A selection of cyclotide sequences and sources
The cyclotide precursor is comprised a hydrophobic Signal peptide that targets the precursor to the Endoplasmic Reticulum (ER), an N-terminal propeptide that then targets it to the vacuole , a cyclotide domain and a final C-terminal propeptide necessary for cyclisation.The cyclotide domain folds in the ER, after which it is trafficked to the vacuole and the cyclotide domain is cyclised by an asperginyl endopeptidase . ( PDB : 1WN8 , 1NB1 ​) [ 17 ]
Kalata (2002) by Julian Voss-Andreae . The pictured sculpture is based on the atomic coordinates of kalata B1. [ 27 ]
A tea made from the plant Oldenlandia affinis was used by an African tribe to induce labor and facilitate childbirth