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Cyclotides: Plant Defense Toxins

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Plant Toxins

Part of the book series: Toxinology ((TOXI))

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Abstract

Cyclotides are plant-derived miniproteins that are exceptionally stable and have a wide range of biological activities, with their principal function thought to be in plant defense. Their putative defense-related activities include insecticidal, anthelmintic, molluscicidal, cytotoxic, and antimicrobial. This article offers insights into the mechanism of action of their various toxic activities and includes a discussion of target organisms and cell lines, with the corresponding lethality/inhibitory concentrations. The article provides an overview on the discovery and applications of cyclotides, mainly in the pharmaceutical and agricultural fields, with a greater emphasis on the latter. The article also covers the various currently used approaches to cyclotide synthesis, focusing on those that potentially can be used for commercially exploiting cyclotides to produce novel pest control agents.

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References

  • Austin J, Wang W, Puttamadappa S, Shekhtman A, Camarero JA. Biosynthesis and biological screening of a genetically encoded library based on the cyclotide MCoTI-I. Chembiochem. 2009;10:2663–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbeta BL, Marshall AT, Gillon AD, Craik DJ, Anderson MA. Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae. Proc Natl Acad Sci U S A. 2008;105:1221–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barry DG, Daly NL, Bokesch HR, Gustafson KR, Craik DJ. Solution structure of the cyclotide palicourein: implications for the development of a pharmaceutical framework. Structure. 2004;12:85–94.

    Article  CAS  PubMed  Google Scholar 

  • Bokesch HR, Pannell LK, Cochran PK, Sowder 2nd RC, McKee TC, Boyd MR. A novel anti-HIV macrocyclic peptide from Palicourea condensata. J Nat Prod. 2001;64:249–50.

    Article  CAS  PubMed  Google Scholar 

  • Bravo A, Gill SS, Soberón M. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control. Toxicon. 2007;49:423–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broussalis AM, Clemente S, Ferraro GE. Hybanthus parviflorus (Violaceae): insecticidal activity of a South American plant. Crop Prot. 2010;29:953–6.

    Article  CAS  Google Scholar 

  • Burman R, Herrmann A, Tran R, Kivela JE, Lomize A, Gullbo J, et al. Cytotoxic potency of small macrocyclic knot proteins: structure-activity and mechanistic studies of native and chemically modified cyclotides. Org Biomol Chem. 2011;9:4306–14.

    Article  CAS  PubMed  Google Scholar 

  • Camarero JA, Tran AT, Kwon Y. Biosynthesis of the cyclotide kalata B1 using protein splicing. Protein Sci. 2004;13:973–6.

    Google Scholar 

  • Camarero JA, Kimura RH, Woo Y-H, Shekhtman A, Cantor J. Biosynthesis of a fully functional cyclotide inside living bacterial cells. Chembiochem. 2007;8:1363–6.

    Article  CAS  PubMed  Google Scholar 

  • Cĕmažar M, Kwon S, Mahatmanto T, Ravipati AS, Craik DJ. Discovery and applications of disulfide-rich cyclic peptides. Curr Top Med Chem. 2012;12:1534–45.

    Article  PubMed  Google Scholar 

  • Chen B, Colgrave ML, Daly NL, Rosengren KJ, Gustafson KR, Craik DJ. Isolation and characterization of novel cyclotides from Viola hederaceae: solution structure and anti-HIV activity of vhl-1, a leaf-specific expressed cyclotide. J Biol Chem. 2005;280:22395–405.

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Colgrave ML, Wang C, Craik DJ. Cycloviolacin H4, a hydrophobic cyclotide from Viola hederaceae. J Nat Prod. 2006;69:23–8.

    Article  CAS  PubMed  Google Scholar 

  • Clark RJ, Daly NL, Craik DJ. Structural plasticity of the cyclic-cystine-knot framework: implications for biological activity and drug design. Biochem J. 2006;394:85–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colgrave ML, Kotze AC, Huang YH, O’Grady J, Simonsen SM, Craik DJ. Cyclotides: natural, circular plant peptides that possess significant activity against gastrointestinal nematode parasites of sheep. Biochemistry. 2008a;47:5581–9.

    Article  CAS  PubMed  Google Scholar 

  • Colgrave ML, Kotze AC, Ireland DC, Wang CK, Craik DJ. The anthelmintic activity of the cyclotides: natural variants with enhanced activity. Chembiochem. 2008b;9:1939–45.

    Article  CAS  PubMed  Google Scholar 

  • Colgrave ML, Kotze AC, Kopp S, McCarthy JS, Coleman GT, Craik DJ. Anthelmintic activity of cyclotides: in vitro studies with canine and human hookworms. Acta Trop. 2009;109:163–6.

    Article  CAS  PubMed  Google Scholar 

  • Craik DJ. Plant cyclotides: circular, knotted peptide toxins. Toxicon. 2001;39:1809–13.

    Article  CAS  PubMed  Google Scholar 

  • Craik DJ. Host-defense activities of cyclotides. Toxins. 2012;4:139–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craik DJ, Daly NL, Bond T, Waine C. Plant cyclotides: a unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J Mol Biol. 1999;294:1327–36.

    Article  CAS  PubMed  Google Scholar 

  • Craik DJ, Anderson MA, Barry DG, Clark RJ, Daly NL, Jennings CV, et al. Discovery and structures of the cyclotides: novel macrocyclic peptides from plants. Lett Pept Sci. 2002;8:119–28.

    Google Scholar 

  • Craik DJ, Daly NL, Mulvenna J, Plan MR, Trabi M. Discovery, structure and biological activities of the cyclotides. Curr Protein Pept Sci. 2004;5:297–315.

    Article  CAS  PubMed  Google Scholar 

  • Craik DJ, Mylne JS, Daly NL. Cyclotides: macrocyclic peptides with applications in drug design and agriculture. Cell Mol Life Sci. 2010;67:9–16.

    Article  CAS  PubMed  Google Scholar 

  • Daly NL, Koltay A, Gustafson KR, Boyd MR, Casas-Finet JR, Craik DJ. Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity. J Mol Biol. 1999a;285:333–45.

    Article  CAS  PubMed  Google Scholar 

  • Daly NL, Love S, Alewood PF, Craik DJ. Chemical synthesis and folding pathways of large cyclic polypeptides: studies of the cystine knot polypeptide kalata B1. Biochemistry. 1999b;38:10606–14.

    Article  CAS  PubMed  Google Scholar 

  • Daly NL, Gustafson KR, Craik DJ. The role of the cyclic peptide backbone in the anti-HIV activity of the cyclotide kalata B1. FEBS Lett. 2004;574:69–72.

    Article  CAS  PubMed  Google Scholar 

  • Daly NL, Clark RJ, Plan MR, Craik DJ. Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif. Biochem J. 2006;393:619–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daly NL, Thorstholm L, Greenwood KP, King GJ, Rosengren KJ, Heras B, et al. Structural insights into the role of the cyclic backbone in a squash trypsin inhibitor. J Biol Chem. 2013;288:36141–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding X, Bai D, Qian J. Novel cyclotides from Hedyotis biflora inhibit proliferation and migration of pancreatic cancer cell in vitro and in vivo. Med Chem Res. 2014;23:1406–13.

    Article  CAS  Google Scholar 

  • Dörnenburg H. Plant cell culture technology – harnessing a biological approach for competitive cyclotides production. Biotechnol Lett. 2008;30:1311–21.

    Article  PubMed  CAS  Google Scholar 

  • Dörnenburg H. Progress in kalata peptide production via plant cell bioprocessing. Biotechnol J. 2009;4:632–45.

    Article  PubMed  CAS  Google Scholar 

  • Dörnenburg H, Frickinger P, Seydel P. Plant cell-based processes for cyclotides production. J Biotechnol. 2008;135:123–6.

    Article  PubMed  CAS  Google Scholar 

  • Felizmenio-Quimio ME, Daly NL, Craik DJ. Circular proteins in plants: solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis. J Biol Chem. 2001;276:22875–82.

    Article  CAS  PubMed  Google Scholar 

  • Fensterseifer IC, Silva ON, Malik U, Ravipati AS, Novaes NR, Miranda PR, et al. Effects of cyclotides against cutaneous infections caused by Staphylococcus aureus. Peptides. 2015;63:38–42.

    Article  CAS  PubMed  Google Scholar 

  • Garcia AE, Camarero JA. Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics. Curr Mol Pharmacol. 2010;3:153–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerlach SL, Burman R, Bohlin L, Mondal D, Göransson U. Isolation, characterization, and bioactivity of cyclotides from the Micronesian plant Psychotria leptothyrsa. J Nat Prod. 2010a;73:1207–13.

    Article  CAS  PubMed  Google Scholar 

  • Gerlach SL, Rathinakumar R, Chakravarty G, Göransson U, Wimley WC, Darwin SP, et al. Anticancer and chemosensitizing abilities of cycloviolacin O2 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers. 2010b;94:617–25.

    Article  CAS  PubMed  Google Scholar 

  • Gerlach SL, Mondal D. The bountiful biological activities of cyclotides. CYS. 2012;3:169–77.

    CAS  Google Scholar 

  • Gerlach SL, Yeshak M, Göransson U, Roy U, Izadpanah R, Mondal D. Cycloviolacin O2 (CyO2) suppresses productive infection and augments the antiviral efficacy of nelfinavir in HIV-1 infected monocytic cells. Biopolymers. 2013;100:471–9.

    Article  CAS  PubMed  Google Scholar 

  • Göransson U, Sjogren M, Svangård E, Claeson P, Bohlin L. Reversible antifouling effect of the cyclotide cycloviolacin O2 against barnacles. J Nat Prod. 2004a;67:1287–90.

    Article  PubMed  CAS  Google Scholar 

  • Göransson U, Svangård E, Claeson P, Bohlin L. Novel strategies for isolation and characterization of cyclotides: the discovery of bioactive macrocyclic plant polypeptides in the Violaceae. Curr Protein Pept Sci. 2004b;5:317–29.

    Article  PubMed  Google Scholar 

  • Gran L. On the effect of a polypeptide isolated from “Kalata-Kalata” (Oldenlandia affinis DC) on the oestrogen dominated uterus. Acta Pharmacol Toxicol. 1973;33:400–8.

    Article  CAS  Google Scholar 

  • Gran L, Sletten K, Skjeldal L. Cyclic peptides from Oldenlandia affinis DC. Molecular and biological properties. Chem Biodivers. 2008;5:2014–22.

    Article  CAS  PubMed  Google Scholar 

  • Gruber CW. Global cyclotide adventure: a journey dedicated to the discovery of circular peptides from flowering plants. Biopolymers. 2010;94:565–72.

    Article  CAS  PubMed  Google Scholar 

  • Gruber CW, Cĕmažar M, Anderson MA, Craik DJ. Insecticidal plant cyclotides and related cystine knot toxins. Toxicon. 2007;49:561–75.

    Article  CAS  PubMed  Google Scholar 

  • Gruber CW, Elliott AG, Ireland DC, Delprete PG, Dessein S, Göransson U, et al. Distribution and evolution of circular miniproteins in flowering plants. Plant Cell. 2008;20:2471–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gustafson KR, Sowder RCI, Henderson LE, Parsons IC, Kashman Y, Cardellina JHI, et al. Circulins A and B: novel HIV-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia. J Am Chem Soc. 1994;116:9337–8.

    Article  CAS  Google Scholar 

  • Gustafson KR, Walton LK, Sowder RCI, Johnson DG, Pannell LK, Cardellina JHI, et al. New circulin macrocyclic polypeptides from Chassalia parvifolia. J Nat Prod. 2000;63:176–8.

    Article  CAS  PubMed  Google Scholar 

  • Hallock YF, Sowder RCI, Pannell LK, Hughes CB, Johnson DG, Gulakowski R, et al. Cycloviolins A-D, anti-HIV macrocyclic peptides from Leonia cymosa. J Org Chem. 2000;65:124–8.

    Article  CAS  PubMed  Google Scholar 

  • He W, Chan LY, Zeng G, Daly NL, Craik DJ, Tan N. Isolation and characterization of cytotoxic cyclotides from Viola philippica. Peptides. 2011;32:1719–23.

    Article  CAS  PubMed  Google Scholar 

  • Heitz A, Hernandez JF, Gagnon J, Hong TT, Pham TT, Nguyen TM, et al. Solution structure of the squash trypsin inhibitor MCoTI-II. A new family for cyclic knottins. Biochemistry. 2001;40:7973–83.

    Article  CAS  PubMed  Google Scholar 

  • Henriques ST, Huang YH, Castanho MARB, Bagatolli LA, Sonza S, Tachedjian G, et al. Phosphatidylethanolamine binding is a conserved feature of cyclotide-membrane interactions. J Biol Chem. 2012;287:33629–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henriques ST, Huang YH, Chaousis S, Wang CK, Craik DJ. Anticancer and toxic properties of cyclotides are dependent on phosphatidylethanolamine phospholipid targeting. Chembiochem. 2014;15:1956–65.

    Article  CAS  Google Scholar 

  • Herrmann A, Burman R, Mylne JS, Karlsson G, Gullbo J, Craik DJ, et al. The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity. Phytochemistry. 2008;69:939–52.

    Article  CAS  PubMed  Google Scholar 

  • Huang YH, Colgrave ML, Clark RJ, Kotze AC, Craik DJ. Lysine-scanning mutagenesis reveals a previously unidentified amendable face of the cyclotide kalata B1 for the optimisation of nematocidal activity. J Biol Chem. 2010;285:10797–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ireland DC, Colgrave ML, Craik DJ. A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability. Biochem J. 2006;400:1–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ireland DC, Wang CK, Wilson JA, Gustafson KR, Craik DJ. Cyclotides as natural anti-HIV agents. Biopolymers. 2008;90:51–60.

    Article  CAS  PubMed  Google Scholar 

  • Ireland DC, Clark RJ, Daly NL, Craik DJ. Isolation, sequencing, and structure-activity relationships of cyclotides. J Nat Prod. 2010;73:1610–22.

    Article  CAS  PubMed  Google Scholar 

  • Jagadish K, Gould A, Borra R, Majumder S, Mushtaq Z, Shekhtman AC, Camarero JA. Recombinant expression and phenotypic screening of a bioactive cyclotide against α-synuclein-induced cytotoxicity in baker’s yeast. Angew Chem Int Ed. 2015;54:1–6.

    Article  CAS  Google Scholar 

  • Jennings C, West J, Waine C, Craik D, Anderson M. Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affinis. Proc Natl Acad Sci U S A. 2001;98:10614–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jennings CV, Rosengren KJ, Daly NL, Plan M, Stevens J, Scanlon MJ, et al. Isolation, solution structure, and insecticidal activity of kalata B2, a circular protein with a twist: do Möbius strips exist in nature? Biochemistry. 2005;44:851–60.

    Article  CAS  PubMed  Google Scholar 

  • Kimura RH, Tran A-T, Camarero JA. Biosynthesis of the cyclotide kalata B1 by using protein splicing. Angew Chem Int Ed. 2006;118:987–90.

    Article  Google Scholar 

  • Lindholm P, Göransson U, Johansson S, Claeson P, Gulbo J, Larsson R, et al. Cyclotides: a novel type of cytotoxic agents. Mol Cancer Ther. 2002;1:365–9.

    CAS  PubMed  Google Scholar 

  • Malagón D, Botterill B, Gray DJ, Lovas E, Duke M, Gray C, et al. Anthelminthic activity of the cyclotides (kalata B1 and B2) against schistosome parasites. Biopolymers. 2013;100:461–70.

    Article  PubMed  CAS  Google Scholar 

  • Mulvenna JP, Sando L, Craik DJ. Processing of a 22 kDa precursor protein to produce the circular protein tricyclon A. Structure. 2005;13:691–701.

    Article  CAS  PubMed  Google Scholar 

  • Mylne JS, Chan LY, Chanson AH, Daly NL, Schaefer H, Bailey TL, et al. Cyclic peptides arising by evolutionary parallelism via asparaginyl-endopeptidase-mediated biosynthesis. Plant Cell. 2012;24:2765–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nair SS, Romanuka J, Billeter M, Skjeldal L, Emmett MR, Nilsson CL, et al. Structural characterization of an unusually stable cyclic peptide, kalata B2 from Oldenlandia affinis. Biochim Biophys Acta. 2006;1764:1568–76.

    Article  CAS  PubMed  Google Scholar 

  • Nguyen GKT, Zhang S, Ngan TKN, Phuong QTN, Chiu MS, Hardjojo A, et al. 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. 2011a;286:24275–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen GKT, Zhang S, Wang W, Wong CTT, Ngan TKN, Tam JP. Discovery of a linear cyclotide from the bracelet subfamily and its disulfide mapping by top-down mass spectrometry. J Biol Chem. 2011b;286:44833–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen GKT, Lian YL, Pang EWH, Phuong QTN, Tran TD, Tam JP. Discovery of linear cyclotides in monocot plant Panicum laxum of Poaceae family provides new insights into evolution and distribution of cyclotides in plants. J Biol Chem. 2013;288:3370–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ovesen RG, Brandt KK, Göransson U, Nielsen J, Hansen HC, Cedergreen N. Biomedicine in the environment: cyclotides constitute potent natural toxins in plants and soil bacteria. Environ Toxicol Chem. 2011;30:1190–6.

    Article  CAS  PubMed  Google Scholar 

  • Park S, Strömstedt AA, Göransson U. Cyclotide structure–activity relationships: qualitative and quantitative approaches linking cytotoxic and anthelmintic activity to the clustering of physicochemical forces. PLoS ONE. 2014;9:e91430.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pinto MFS, Fensterseifer ICM, Migliolo L, Sousa DA, de Capdville G, Arboleda-Valencia JW, et al. Identification and structural characterization of novel cyclotide with activity against an insect pest of sugar cane. J Biol Chem. 2012;287:134–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plan MRR, Göransson U, Clark RJ, Daly NL, Colgrave ML, Craik DJ. The cyclotide fingerprint in Oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides. Chembiochem. 2007;8:1001–11.

    Article  CAS  PubMed  Google Scholar 

  • Plan MRR, Saska I, Cagauan AG, Craik DJ. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (Golden Apple Snail). J Agric Food Chem. 2008;56:5237–41.

    Article  CAS  PubMed  Google Scholar 

  • Plan MRR, Rosengren KJ, Sando L, Daly NL, Craik DJ. Structural and biochemical characteristics of the cyclotide kalata B5 from Oldenlandia affinis. Biopolymers. 2010;94:647–58.

    Article  CAS  PubMed  Google Scholar 

  • Poth AG, Colgrave ML, Lyons RE, Daly NL, Craik DJ. Discovery of an unusual biosynthetic origin for circular proteins in legumes. Proc Natl Acad Sci U S A. 2011a;108:10127–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poth AG, Colgrave ML, Philip R, Kerenga B, Daly NL, Anderson MA, et al. Discovery of cyclotides in the Fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins. ACS Chem Biol. 2011b;6:345–55.

    Article  CAS  PubMed  Google Scholar 

  • Poth AG, Mylne JS, Grassl J, Lyons RE, Millar AH, Colgrave ML, et al. Cyclotides associate with leaf vasculature and are the products of a novel precursor in petunia (Solanaceae). J Biol Chem. 2012;287:27033–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poth AG, Chan LY, Craik DJ. Cyclotides as grafting frameworks for protein engineering and drug design applications. Biopolymers. 2013;100:480–91.

    Article  CAS  PubMed  Google Scholar 

  • Pränting M, Loov C, Burman R, Göransson U, Andersson DI. The cyclotide cycloviolacin O2 from Viola odorata has potent bactericidal activity against Gram-negative bacteria. J Antimicrob Chemother. 2010;65:1964–71.

    Article  PubMed  CAS  Google Scholar 

  • Saether O, Craik DJ, Campbell ID, Sletten K, Juul J, Norman DG. Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. Biochemistry. 1995;34:4147–58.

    Article  CAS  PubMed  Google Scholar 

  • Suryawanshi R, Patil C, Borase H, Narkhede C, Patil S. Screening of Rubiaceae and Apocynaceae extracts for mosquito larvicidal potential. Nat Prod Res. 2015;29:353–8.

    Article  CAS  PubMed  Google Scholar 

  • Svangård E, Göransson U, Hocaoglu Z, Gullbo J, Larsson R, Claeson P, et al. Cytotoxic cyclotides from Viola tricolor. J Nat Prod. 2004;67:144–7.

    Article  PubMed  CAS  Google Scholar 

  • Svangård E, Burman R, Gunasekera S, Lovborg H, Gullbo J, Göransson U. Mechanism of action of cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes. J Nat Prod. 2007;70:643–7.

    Article  PubMed  CAS  Google Scholar 

  • Tam JP, Lu Y-A. Synthesis of large cyclic cystine-knot peptide by orthogonal coupling strategy using unprotected peptide precursors. Tetrahedron Lett. 1997;38:5599–602.

    Article  CAS  Google Scholar 

  • Tam JP, Lu Y-A. A biomimetic strategy in the synthesis and fragmentation of cyclic protein. Protein Sci. 1998;7:1583–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tam JP, Lu Y-A, Yu Q. Thia zip reaction for synthesis of large cyclic peptides: mechanisms and applications. J Am Chem Soc. 1999a;121:4316–24.

    Article  CAS  Google Scholar 

  • Tam JP, Lu YA, Yang JL, Chiu KW. An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides. Proc Natl Acad Sci U S A. 1999b;96:8913–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang J, Wang CK, Pan X, Yan H, Zeng G, Xu W, et al. Isolation and characterization of cytotoxic cyclotides from Viola tricolor. Peptides. 2010a;31:1434–40.

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Wang CK, Pan X, Yan H, Zeng G, Xu W, et al. Isolation and characterization of bioactive cyclotides from Viola labridorica. Helv Chim Acta. 2010b;93:2287–95.

    Article  CAS  Google Scholar 

  • Thongyoo P, Tate EW, Leatherbarrow RJ. Total synthesis of the macrocyclic cysteine knot microprotein MCoTI-II. Chem Commun. 2006:2848–2850

    Google Scholar 

  • Thongyoo P, Jaulent AM, Tate EW, Leatherbarrow RJ. Immobilized protease-assisted synthesis of engineered cysteine-knot microproteins. Chembiochem. 2007;8:1107–9.

    Article  CAS  PubMed  Google Scholar 

  • Thongyoo P, Roque-Rosell N, Leatherbarrow RJ, Tate EW. Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides. Org Biomol Chem. 2008;6:1462–70.

    Article  CAS  PubMed  Google Scholar 

  • Thongyoo P, Bonomelli C, Leatherbarrow RJ, Tate EW. Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold. J Med Chem. 2009;52:6197–200.

    Article  CAS  PubMed  Google Scholar 

  • Trabi M, Craik DJ. Tissue-specific expression of head-to-tail cyclized miniproteins in Violaceae and structure determination of the root cyclotide Viola hederacea root cyclotide1. Plant Cell. 2004;16:2204–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang CK, Colgrave ML, Gustafson KR, Ireland DC, Göransson U, Craik DJ. Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis. J Nat Prod. 2008;71:47–52.

    Article  CAS  PubMed  Google Scholar 

  • Wang CK, Colgrave ML, Ireland DC, Kaas Q, Craik DJ. Despite a conserved cystine knot motif, different cyclotides have different membrane binding modes. Biophys J. 2009a;97:1471–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang CK, Hu SH, Martin JL, Sjogren T, Hajdu J, Bohlin L, et al. Combined X-ray and NMR analysis of the stability of the cyclotide cystine knot fold that underpins its insecticidal activity and potential use as a drug scaffold. J Biol Chem. 2009b;284:10672–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang CK, Clark RJ, Harvey PJ, Rosengren KJ, Cĕmažar M, Craik DJ. The role of conserved Glu residue on cyclotide stability and activity: a structural and functional study of kalata B12, a naturally occurring Glu to Asp mutant. Biochemistry. 2011;50:4077–86.

    Article  CAS  PubMed  Google Scholar 

  • Wang CK, King GJ, Northfield SE, Ojeda PG, Craik DJ. Racemic and quasi-racemic X-ray structures of cyclic disulfide-rich peptide drug scaffolds. Angew Chem Int Ed. 2014;53:11236–41.

    Article  CAS  Google Scholar 

  • Whiterup KM, Bogusky MJ, Anderson PS, Ramjit H. Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated from Psychotria longipes. J Nat Prod. 1994;57:1619–25.

    Article  Google Scholar 

  • Yeshak MY, Burman R, Asres K, Göransson U. Cyclotides from an extreme habitat: characterization of cyclic peptides from Viola abyssinica of the Ethiopian highlands. J Nat Prod. 2011;74:727–31.

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Xiao KZ, Jin J, Zhang Y, Zhou W. Chemosensitizing activities of cyclotides from Clitoria ternatea in paclitaxel-resistant lung cancer cells. Oncol Lett. 2013;5:641–4.

    CAS  Google Scholar 

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Acknowledgments

Work in our laboratory on cyclotides is funded by grants from the Australian Research Council (DP150100443) and the National Health and Medical Research Council (NHMRC; APP1047857). DJC is an NHMRC Professorial Fellow (APP1026501).

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Authors and Affiliations

  1. Institute for Molecular Bioscience, The University of Queensland, 4072, Brisbane, Qld, Australia

    Georgianna Kae Oguis, Meng-Wei Kan & David J Craik

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  1. Georgianna Kae Oguis
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  2. Meng-Wei Kan
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  3. David J Craik
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Correspondence to David J Craik .

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Editors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Brain Institute – InsCer Pontificia Universidade Católica do Rio, Universidade Federal do Rio Grande do Su Centro de Biotecnologia, Porto Alegre, RS, Brazil

    Célia R. Carlini

  3. Centro de Biotecnologia, Universidade Federal do Rio Grande do Su, Porto Alegre, RS, Brazil

    Rodrigo Ligabue-Braun

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Oguis, G.K., Kan, MW., Craik, D.J. (2015). Cyclotides: Plant Defense Toxins. In: Gopalakrishnakone, P., Carlini, C., Ligabue-Braun, R. (eds) Plant Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6728-7_7-1

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  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6728-7

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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