Cliotide

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 butelase 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]

  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. doi:10.1074/jbc.m111.229922. PMC 3129208. PMID 21596752.
  2. ^ Nguyen, Kien Truc Giang; Zhang, S; Nguyen, N. T.; Nguyen, P. Q.; Chiu, M. S.; Hardjojo, A.; Tam, J. P. (8 July 2011). "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. 286 (27): 24275–24287. doi:10.1074/jbc.M111.229922. PMC 3129208. PMID 21596752. Retrieved July 8, 2011.
  3. ^ Nguyen KN, Nguyen GK, Nguyen PQ, Ang KH, Dedon PC, Tam JP (2016). "Immunostimulating and Gram-negative-specific Antibacterial Cyclotides from the Butterfly Pea Clitoria ternatea". FEBS J. 283 (11): 2067–2090. doi:10.1111/febs.13720. PMID 27007913.
  4. ^ a b Gilding, Edward K.; Jackson, Mark A.; Poth, Aaron G.; Henriques, Sónia Troeira; Prentis, Peter J.; Mahatmanto, Tunjung; Craik, David J. (December 2015). "Gene coevolution and regulation lock cyclic plant defence peptides to their targets" (PDF). New Phytologist. 210 (2): 717–30. doi:10.1111/nph.13789. PMID 26668107.
  5. ^ Poth, A. G.; Colgrave, M. L.; Lyons, R. E.; Daly, N. L.; Craik, D. J. (18 May 2011). "Discovery of an unusual biosynthetic origin for circular proteins in legumes". Proceedings of the National Academy of Sciences. 108 (25): 10127–10132. Bibcode:2011PNAS..10810127P. doi:10.1073/pnas.1103660108. PMC 3121837. PMID 21593408.
  6. ^ Nguyen, Giang (2014). "Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis". Nature Chemical Biology. 10 (9): 732–738. doi:10.1038/nchembio.1586. hdl:10220/38787. PMID 25038786.