Cliotide Explained

Cliotides are a group of related peptides that have been isolated from the heat-stable fraction of Clitoria ternatea (Cliotides) extracts.^[1] Cliotides belong to a larger classification of peptides, the cyclotides.

Preliminary studies show that cliotides display a variety of biochemical properties which have attracted scientific interest in the possibility of developing antimicrobial and anti-cancer agents from them.

Cliotides display in vitro antimicrobial activity against E. coli, K. pneumoniae, and P. aeruginosa and cytotoxicity against HeLa cells.^[2]

Cliotides also possess immunostimulating activity. At a concentration of 1 μM, cationic cliotides are capable of augmenting the secretion of various cytokines and chemokines in human monocytes at both resting and LPS-stimulated states.^[3] Chemokines such as RANTES, MIP-1β, MIP-1α, IP-10, IL-8 and TNF-α were among the most upregulated with up to 129-fold increase in secretion level.

Different cyclotides have protein sequences which engender different biophysical and functional properties, to be expressed in different organs.^[4] For example, cyclotides from aerial organs possess tighter binding activity to insect-like membranes, whereas cyclotides from roots and seed, two organs that contact soil, have relatively higher effectiveness against juveniles of the model nematode Caenorhabditis elegans.^[4] The isolated Cter M cyclotide that is highly expressed in aerial organs was shown to effectively slow the growth and kill moth larvae.^[5]

The enzyme responsible for the biosynthesis and backbone cyclization of cliotides has recently been isolated. It was named 1 in accordance with its local name in Malaysia and Singapore (bunga telang ligase). Butelase 1 is the fastest peptide ligase known capable of catalyzing peptide cyclization at an extraordinary efficiency.^[6]

Notes and References

1. Nguyen . GK . Zhang . S . Nguyen . NT . Nguyen . PQ . Chiu . MS . Hardjojo . A . Tam . JP. . Jul 2011 . Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of albumin-1 chain a and cyclotide domains in the Fabaceae family . J Biol Chem . 286 . 27. 24275–87 . 10.1074/jbc.m111.229922. 21596752 . 3129208. free .
2. Nguyen. Kien Truc Giang. Zhang, S . Nguyen, N. T. . Nguyen, P. Q. . Chiu, M. S. . Hardjojo, A. . Tam, J. P. . Discovery and Characterization of Novel Cyclotides Originated from Chimeric Precursors Consisting of Albumin-1 Chain a and Cyclotide Domains in the Fabaceae Family. Journal of Biological Chemistry. 8 July 2011. 286. 27. 24275–24287. 10.1074/jbc.M111.229922. July 8, 2011. 21596752. 3129208. free.
3. FEBS J . 2016 . 10.1111/febs.13720 . 27007913 . Immunostimulating and Gram-negative-specific Antibacterial Cyclotides from the Butterfly Pea Clitoria ternatea . Nguyen KN, Nguyen GK, Nguyen PQ, Ang KH, Dedon PC, Tam JP . 283 . 11 . 2067–2090. free .
4. Gilding . Edward K. . Jackson . Mark A. . Poth . Aaron G. . Henriques . Sónia Troeira . Prentis . Peter J. . Mahatmanto . Tunjung . Craik . David J. . Gene coevolution and regulation lock cyclic plant defence peptides to their targets. New Phytologist . 210 . 2 . December 2015 . 717–30. 10.1111/nph.13789. 26668107 .
5. Poth . A. G. . Colgrave . M. L. . Lyons . R. E. . Daly . N. L. . Craik . D. J. . Discovery of an unusual biosynthetic origin for circular proteins in legumes. Proceedings of the National Academy of Sciences . 18 May 2011 . 108 . 25 . 10127–10132 . 10.1073/pnas.1103660108. 2011PNAS..10810127P . 21593408 . 3121837. free .
6. Nguyen. Giang. Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis. Nature Chemical Biology. 10. 9. 732–738. 10.1038/nchembio.1586. 25038786. 2014. 10220/38787 . free.