cliotide

Cliotides are a group of related peptides that have been isolated from the heat-stable fraction of Clitoria ternatea (Cliotides) extracts.{{cite journal | last1 = Nguyen | first1 = GK | last2 = Zhang | first2 = S | last3 = Nguyen | first3 = NT | last4 = Nguyen | first4 = PQ | last5 = Chiu | first5 = MS | last6 = Hardjojo | first6 = A | last7 = Tam | first7 = JP. |date=Jul 2011 | title = Discovery and characterization of novel cyclotides originated from chimeric precursors consisting of albumin-1 chain a and cyclotide domains in the Fabaceae family | journal = J Biol Chem | volume = 286 | issue = 27| pages = 24275–87 | doi=10.1074/jbc.m111.229922| pmid = 21596752 | pmc=3129208| doi-access = free }} 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.{{cite journal|last=Nguyen|first=Kien Truc Giang|author2=Zhang, S |author3=Nguyen, N. T. |author4=Nguyen, P. Q. |author5=Chiu, M. S. |author6=Hardjojo, A. |author7= Tam, J. P. |title=Discovery and Characterization of Novel Cyclotides Originated from Chimeric Precursors Consisting of Albumin-1 Chain a and Cyclotide Domains in the Fabaceae Family|journal=Journal of Biological Chemistry|date=8 July 2011|volume=286|issue=27|pages=24275–24287|doi=10.1074/jbc.M111.229922|url=http://www.jbc.org/content/286/27/24275.abstract|accessdate=July 8, 2011|pmid=21596752|pmc=3129208|doi-access=free}}

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.{{cite journal | journal = FEBS J | date = 2016 | doi = 10.1111/febs.13720 | pmid = 27007913 | title = Immunostimulating and Gram-negative-specific Antibacterial Cyclotides from the Butterfly Pea Clitoria ternatea |vauthors=Nguyen KN, Nguyen GK, Nguyen PQ, Ang KH, Dedon PC, Tam JP | volume=283 | issue = 11 | pages=2067–2090| doi-access = free }} 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.{{cite journal |last1=Gilding |first1=Edward K. |last2=Jackson |first2=Mark A. |last3=Poth |first3=Aaron G. |last4=Henriques |first4=Sónia Troeira |last5=Prentis |first5=Peter J. |last6=Mahatmanto |first6=Tunjung |last7=Craik |first7=David J. |title=Gene coevolution and regulation lock cyclic plant defence peptides to their targets|journal=New Phytologist |volume=210 |issue=2 |date=December 2015 |pages= 717–30|doi=10.1111/nph.13789|pmid=26668107 |url=https://espace.library.uq.edu.au/view/UQ:376489/Gilding_2016_NewPhytol_210_717_cv585.pdf }} 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. The isolated Cter M cyclotide that is highly expressed in aerial organs was shown to effectively slow the growth and kill moth larvae.{{cite journal |last1=Poth |first1=A. G. |last2=Colgrave |first2=M. L. |last3=Lyons |first3=R. E. |last4=Daly |first4=N. L. |last5=Craik |first5=D. J. |title=Discovery of an unusual biosynthetic origin for circular proteins in legumes|journal=Proceedings of the National Academy of Sciences |date=18 May 2011 |volume=108 |issue=25 |pages=10127–10132 |doi=10.1073/pnas.1103660108|bibcode=2011PNAS..10810127P |pmid=21593408 |pmc=3121837|doi-access=free }}

The enzyme responsible for the biosynthesis and backbone cyclization of cliotides has recently been isolated. It was named {{chem name|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.{{cite journal|last1=Nguyen|first1=Giang|title=Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis|journal=Nature Chemical Biology|volume=10|issue=9|pages=732–738|doi=10.1038/nchembio.1586|pmid=25038786|year=2014|hdl=10220/38787 |hdl-access=free}}