cyclotides

Summary

Summary: A continuous circle of peptide bonds, typically of 2-3 dozen AMINO ACIDS, so there is no free N- or C-terminus. They are further characterized by six conserved CYSTEINE residues that form CYSTINE KNOT MOTIFS.

Top Publications

  1. Tam J, Lu Y, Yang J, Chiu K. An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides. Proc Natl Acad Sci U S A. 1999;96:8913-8 pubmed
    ..Furthermore, their end-to-end cyclic structure with a cystine-knot motif represents a molecular structure of antimicrobials and may provide a useful template for the design of novel peptide antibiotics. ..
  2. Daly N, Gustafson K, Craik D. The role of the cyclic peptide backbone in the anti-HIV activity of the cyclotide kalata B1. FEBS Lett. 2004;574:69-72 pubmed
    The plant cyclotides, the largest known family of circular proteins, have tightly folded structures and a range of biological activities that lend themselves to potential pharmaceutical and agricultural applications...
  3. Gerlach S, Rathinakumar R, Chakravarty G, Goransson U, Wimley W, Darwin S, et al. Anticancer and chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers. 2010;94:617-25 pubmed publisher
    ..Furthermore, three novel cyclotides (psyle A, C and E) from Psychotria leptothyrsa (Rubiaceae) were also monitored for cytotoxic activity...
  4. Henriques S, Huang Y, Rosengren K, Franquelim H, Carvalho F, Johnson A, et al. Decoding the membrane activity of the cyclotide kalata B1: the importance of phosphatidylethanolamine phospholipids and lipid organization on hemolytic and anti-HIV activities. J Biol Chem. 2011;286:24231-41 pubmed publisher
    b>Cyclotides, a large family of cyclic peptides from plants, have a broad range of biological activities, including insecticidal, cytotoxic, and anti-HIV activities...
  5. Nair S, Romanuka J, Billeter M, Skjeldal L, Emmett M, Nilsson C, et al. Structural characterization of an unusually stable cyclic peptide, kalata B2 from Oldenlandia affinis. Biochim Biophys Acta. 2006;1764:1568-76 pubmed
    ..Infrared multiphoton dissociation establishes the disulfide bond linkages in kalata B2 as I-IV, II-V and III-VI...
  6. Colgrave M, Poth A, Kaas Q, Craik D. A new "era" for cyclotide sequencing. Biopolymers. 2010;94:592-601 pubmed publisher
    In recent years, the discovery of a large family of macrocyclic peptides, the cyclotides, has revealed Natures ingenuity in molecular drug design...
  7. Trabi M, Mylne J, Sando L, Craik D. Circular proteins from Melicytus (Violaceae) refine the conserved protein and gene architecture of cyclotides. Org Biomol Chem. 2009;7:2378-88 pubmed publisher
    b>Cyclotides are cyclic disulfide rich mini-proteins found in various Rubiaceae (coffee family), Violaceae (violet family) and Cucurbitaceae (squash family) plant species...
  8. Mylne J, Wang C, van der Weerden N, Craik D. Cyclotides are a component of the innate defense of Oldenlandia affinis. Biopolymers. 2010;94:635-46 pubmed publisher
    b>Cyclotides are small cysteine-rich plant peptides similar in size and processing to the defensins...
  9. Goransson U, Craik D. Disulfide mapping of the cyclotide kalata B1. Chemical proof of the cystic cystine knot motif. J Biol Chem. 2003;278:48188-96 pubmed
    The cyclotides are a recently discovered family of plant proteins that have the fascinating structural feature of a continuous cyclic backbone and, putatively, a knotted arrangement of their three conserved disulfide bonds...

More Information

Publications90

  1. Simonsen S, Sando L, Ireland D, Colgrave M, Bharathi R, Goransson U, et al. A continent of plant defense peptide diversity: cyclotides in Australian Hybanthus (Violaceae). Plant Cell. 2005;17:3176-89 pubmed
    b>Cyclotides are plant-derived miniproteins that have the unusual features of a head-to-tail cyclized peptide backbone and a knotted arrangement of disulfide bonds...
  2. Combelles C, Gracy J, Heitz A, Craik D, Chiche L. Structure and folding of disulfide-rich miniproteins: insights from molecular dynamics simulations and MM-PBSA free energy calculations. Proteins. 2008;73:87-103 pubmed publisher
    ..Interestingly, a comparison of the free energy components for kalata B1 and MCoTI-II suggests that cyclotides and squash inhibitors, although sharing the same scaffold, are stabilized through different interactions...
  3. Gunasekera S, Daly N, Anderson M, Craik D. Chemical synthesis and biosynthesis of the cyclotide family of circular proteins. IUBMB Life. 2006;58:515-24 pubmed
    b>Cyclotides are a recently discovered class of proteins that have a characteristic head-to-tail cyclized backbone stabilized by a knotted arrangement of three disulfide bonds...
  4. Goransson U, Herrmann A, Burman R, Haugaard Jönsson L, Rosengren K. The conserved glu in the cyclotide cycloviolacin O2 has a key structural role. Chembiochem. 2009;10:2354-60 pubmed publisher
    b>Cyclotides are a large family of plant peptides that are characterised by a head-to-tail circular backbone and three disulfide bonds that are arranged in a cystine knot...
  5. Saether O, Craik D, Campbell I, Sletten K, Juul J, Norman D. Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. Biochemistry. 1995;34:4147-58 pubmed
    ..This structure involves one of the disulfide bonds (5-22) threading through the eight amino acid loop formed by the other two disulfide bonds and the peptide fragments connecting them. ..
  6. Wang C, Colgrave M, Ireland D, Kaas Q, Craik D. Despite a conserved cystine knot motif, different cyclotides have different membrane binding modes. Biophys J. 2009;97:1471-81 pubmed publisher
    b>Cyclotides are cyclic proteins produced by plants for defense against pests. Because of their remarkable stability and diverse bioactivities, they have a range of potential therapeutic applications...
  7. Herrmann A, Burman R, Mylne J, Karlsson G, Gullbo J, Craik D, et al. The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity. Phytochemistry. 2008;69:939-52 pubmed publisher
    The cyclotides are currently the largest known family of head-to-tail cyclic proteins...
  8. Lindholm P, Goransson U, Johansson S, Claeson P, Gullbo J, Larsson R, et al. Cyclotides: a novel type of cytotoxic agents. Mol Cancer Ther. 2002;1:365-9 pubmed
    Cytotoxic activities of three naturally occurring macrocyclic peptides (cyclotides) isolated from the two violets, Viola arvensis Murr. and Viola odorata L., were investigated...
  9. Heitz A, Hernandez J, Gagnon J, Hong T, Pham T, Nguyen T, et al. Solution structure of the squash trypsin inhibitor MCoTI-II. A new family for cyclic knottins. Biochemistry. 2001;40:7973-83 pubmed
    ..These differences might explain why the isolated macrocyclic squash inhibitors from M. cochinchinensis display no significant antibacterial activity, whereas circulins and kalata B1 do. ..
  10. Wang C, Clark R, Harvey P, Rosengren K, Cemazar M, Craik D. 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 pubmed publisher
    b>Cyclotides are a family of plant defense proteins with a unique cyclic backbone and cystine knot...
  11. Huang Y, Colgrave M, Clark R, Kotze A, Craik D. Lysine-scanning mutagenesis reveals an amendable face of the cyclotide kalata B1 for the optimization of nematocidal activity. J Biol Chem. 2010;285:10797-805 pubmed publisher
    b>Cyclotides are a family of macrocyclic peptides that combine the unique features of a head-to-tail cyclic backbone and a cystine knot motif, the combination of which imparts them with extraordinary stability...
  12. Barbeta B, Marshall A, Gillon A, Craik D, Anderson M. Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae. Proc Natl Acad Sci U S A. 2008;105:1221-5 pubmed publisher
    Several members of the Rubiaceae and Violaceae plant families produce a series of cyclotides or macrocyclic peptides of 28-37 aa with an embedded cystine knot...
  13. Barry D, Daly N, Bokesch H, Gustafson K, Craik D. Solution structure of the cyclotide palicourein: implications for the development of a pharmaceutical framework. Structure. 2004;12:85-94 pubmed
    The cyclotides are a family of disulfide-rich proteins from plants. They have the characteristic structural features of a circular protein backbone and a knotted arrangement of disulfide bonds...
  14. Craik D, Daly N, Mulvenna J, Plan M, Trabi M. Discovery, structure and biological activities of the cyclotides. Curr Protein Pept Sci. 2004;5:297-315 pubmed
    The cyclotides are a family of small disulfide rich proteins that have a cyclic peptide backbone and a cystine knot formed by three conserved disulfide bonds...
  15. Daly N, Clark R, Plan M, Craik D. Kalata B8, a novel antiviral circular protein, exhibits conformational flexibility in the cystine knot motif. Biochem J. 2006;393:619-26 pubmed
    The cyclotides are a family of circular proteins with a range of biological activities and potential pharmaceutical and agricultural applications...
  16. Poth A, Mylne J, Grassl J, Lyons R, Millar A, Colgrave M, 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 pubmed publisher
    b>Cyclotides are a large family of plant peptides that are structurally defined by their cyclic backbone and a trifecta of disulfide bonds, collectively known as the cyclic cystine knot (CCK) motif...
  17. Seydel P, Gruber C, Craik D, Dörnenburg H. Formation of cyclotides and variations in cyclotide expression in Oldenlandia affinis suspension cultures. Appl Microbiol Biotechnol. 2007;77:275-84 pubmed
    b>Cyclotides, a family of disulfide-rich mini-proteins, show a wide range of biological activities, making them interesting targets for pharmaceutical and agrochemical applications, but little is known about their natural function and the ..
  18. He W, Chan L, Zeng G, Daly N, Craik D, Tan N. Isolation and characterization of cytotoxic cyclotides from Viola philippica. Peptides. 2011;32:1719-23 pubmed publisher
    b>Cyclotides are a large family of plant peptides characterized by a macrocyclic backbone and knotted arrangement of three disulfide bonds...
  19. Gruber C, Cemazar M, Anderson M, Craik D. Insecticidal plant cyclotides and related cystine knot toxins. Toxicon. 2007;49:561-75 pubmed
    b>Cyclotides are small disulphide-rich peptides found in plants from the violet (Violaceae), coffee (Rubiaceae) and cucurbit (Cucurbitaceae) families...
  20. Conlan B, Colgrave M, Gillon A, Guarino R, Craik D, Anderson M. Insights into processing and cyclization events associated with biosynthesis of the cyclic Peptide kalata B1. J Biol Chem. 2012;287:28037-46 pubmed publisher
    Plant cyclotides are the largest family of gene-encoded cyclic proteins. They act as host defense molecules to protect plants and are promising candidates as insecticidal and nematocidal agents in agriculture...
  21. Simonsen S, Daly N, Craik D. Capped acyclic permutants of the circular protein kalata B1. FEBS Lett. 2004;577:399-402 pubmed
    The cyclotides are a family of head-to-tail cyclized peptides that display exceptionally high stability and a range of biological activities...
  22. Yeshak M, Burman R, Asres K, Goransson U. Cyclotides from an extreme habitat: characterization of cyclic peptides from Viola abyssinica of the Ethiopian highlands. J Nat Prod. 2011;74:727-31 pubmed publisher
    As part of ongoing explorations of the structural diversity of cyclotides, the cyclotide content of a native violet of the East African highlands, Viola abyssinica (which grows at altitudes up to 3400 m), was studied...
  23. Plan M, Saska I, Cagauan A, Craik D. 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 pubmed publisher
    Golden apple snails ( Pomacea canaliculata) are serious pests of rice in South East Asia. Cyclotides are backbone cyclized peptides produced by plants from Rubiaceae and Violaceae...
  24. Craik D, Cemazar M, Daly N. The cyclotides and related macrocyclic peptides as scaffolds in drug design. Curr Opin Drug Discov Devel. 2006;9:251-60 pubmed
    ..b>Cyclotides are macrocyclic cystine-knotted mini-proteins that have a broad range of bioactivities and are exceptionally ..
  25. Gould A, Ji Y, Aboye T, Camarero J. Cyclotides, a novel ultrastable polypeptide scaffold for drug discovery. Curr Pharm Des. 2011;17:4294-307 pubmed
    b>Cyclotides are a unique and growing family of backbone cyclized peptides that also contain a cystine knot motif built from six conserved cysteine residues...
  26. Chan L, Gunasekera S, Henriques S, Worth N, Le S, Clark R, et al. Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. Blood. 2011;118:6709-17 pubmed publisher
    ..This is the first report of using these scaffolds to improve the activity and stability of angiogenic peptide sequences and is a promising approach for promoting angiogenesis for therapeutic uses. ..
  27. Dutton J, Renda R, Waine C, Clark R, Daly N, Jennings C, et al. Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins. J Biol Chem. 2004;279:46858-67 pubmed
    The cyclotides are the largest family of naturally occurring circular proteins. The mechanism by which the termini of these gene-encoded proteins are linked seamlessly with a peptide bond to form a circular backbone is unknown...
  28. Craik D. Discovery and applications of the plant cyclotides. Toxicon. 2010;56:1092-102 pubmed publisher
    The cyclotides are a family of plant-derived proteins that occur in plants from the Violaceae (violet), Rubiaceae (coffee) and Cucurbitaceae (cucurbit) families and have a diverse range of biological activities, including uterotonic, anti-..
  29. Avrutina O, Schmoldt H, Gabrijelcic Geiger D, Le Nguyen D, Sommerhoff C, Diederichsen U, et al. Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II. Biol Chem. 2005;386:1301-6 pubmed
    ..These data suggest that the formation of a circular backbone in the MCoTI squash inhibitors results in enhanced affinity and therefore is a determinant of biological activity. ..
  30. Gruber C. Global cyclotide adventure: a journey dedicated to the discovery of circular peptides from flowering plants. Biopolymers. 2010;94:565-72 pubmed publisher
    ..b>Cyclotides--disulfide-knotted and head-to-tail cyclized plant peptides that exhibit various bioactivities--are by far the ..
  31. Colgrave M, Craik D. Thermal, chemical, and enzymatic stability of the cyclotide kalata B1: the importance of the cyclic cystine knot. Biochemistry. 2004;43:5965-75 pubmed
    The cyclotides constitute a recently discovered family of plant-derived peptides that have the unusual features of a head-to-tail cyclized backbone and a cystine knot core...
  32. Gunasekera S, Foley F, Clark R, Sando L, Fabri L, Craik D, et al. Engineering stabilized vascular endothelial growth factor-A antagonists: synthesis, structural characterization, and bioactivity of grafted analogues of cyclotides. J Med Chem. 2008;51:7697-704 pubmed publisher
    b>Cyclotides are plant derived mini-proteins with compact folded structures and exceptional stability. Their stability derives from a head-to-tail cyclized backbone coupled with a cystine knot arrangement of three-conserved disulfide bonds...
  33. Colgrave M, Kotze A, Ireland D, Wang C, Craik D. The anthelmintic activity of the cyclotides: natural variants with enhanced activity. Chembiochem. 2008;9:1939-45 pubmed publisher
    The cyclotides are a family of backbone-cyclised cystine-knot-containing peptides from plants that possess anthelmintic activity against Haemonchus contortus and Trichostrongylus colubriformis, two important gastrointestinal nematode ..
  34. Tam J, Lu Y. A biomimetic strategy in the synthesis and fragmentation of cyclic protein. Protein Sci. 1998;7:1583-92 pubmed
  35. Daly N, Craik D. Design and therapeutic applications of cyclotides. Future Med Chem. 2009;1:1613-22 pubmed publisher
    b>Cyclotides are plant-derived peptides with a cyclic backbone and knotted topology of disulfide bonds...
  36. Goransson U, Sjögren M, Svangård E, Claeson P, Bohlin L. Reversible antifouling effect of the cyclotide cycloviolacin O2 against barnacles. J Nat Prod. 2004;67:1287-90 pubmed
    ..Cycloviolacin O2 was isolated from the terrestrial plant Viola odorata by strong cation exchange and reversed-phase HPLC and identified by mass spectrometry following aminoethylation and enzymatic cleavage...
  37. Kamimori H, Hall K, Craik D, Aguilar M. Studies on the membrane interactions of the cyclotides kalata B1 and kalata B6 on model membrane systems by surface plasmon resonance. Anal Biochem. 2005;337:149-53 pubmed
  38. Plan M, Goransson U, Clark R, Daly N, Colgrave M, Craik D. The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides. Chembiochem. 2007;8:1001-11 pubmed
    The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised...
  39. Hashempour H, Koehbach J, Daly N, Ghassempour A, Gruber C. Characterizing circular peptides in mixtures: sequence fragment assembly of cyclotides from a violet plant by MALDI-TOF/TOF mass spectrometry. Amino Acids. 2013;44:581-95 pubmed publisher
    b>Cyclotides are a very abundant class of plant peptides that display significant sequence variability around a conserved cystine-knot motif and a head-to-tail cyclized backbone conferring them with remarkable stability...
  40. Wang C, Colgrave M, Gustafson K, Ireland D, Goransson U, Craik D. Anti-HIV cyclotides from the Chinese medicinal herb Viola yedoensis. J Nat Prod. 2008;71:47-52 pubmed
    b>Cyclotides are macrocyclic plant peptides characterized by a knotted arrangement of three disulfide bonds. They display a range of interesting bioactivities, including anti-HIV and insecticidal activities...
  41. Gustafson K, McKee T, Bokesch H. Anti-HIV cyclotides. Curr Protein Pept Sci. 2004;5:331-40 pubmed
    The cyclotides are a recently discovered, structurally unique family of bioactive plant peptides...
  42. Ovesen R, Brandt K, Goransson U, Nielsen J, Hansen H, Cedergreen N. Biomedicine in the environment: cyclotides constitute potent natural toxins in plants and soil bacteria. Environ Toxicol Chem. 2011;30:1190-6 pubmed publisher
    ..b>Cyclotides are gene-encoded, circular, cystine-rich mini-proteins produced in Violaceae and Rubiaceae in high amounts...
  43. Mulvenna J, Sando L, Craik D. Processing of a 22 kDa precursor protein to produce the circular protein tricyclon A. Structure. 2005;13:691-701 pubmed
    b>Cyclotides are a family of plant proteins that have the unusual combination of head-to-tail backbone cyclization and a cystine knot motif...
  44. Aboye T, Clark R, Burman R, Roig M, Craik D, Goransson U. Interlocking disulfides in circular proteins: toward efficient oxidative folding of cyclotides. Antioxid Redox Signal. 2011;14:77-86 pubmed publisher
    b>Cyclotides are ultrastable plant proteins characterized by the presence of a cyclic amide backbone and three disulfide bonds that form a cystine knot...
  45. Koehbach J, O Brien M, Muttenthaler M, Miazzo M, Akcan M, Elliott A, et al. Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proc Natl Acad Sci U S A. 2013;110:21183-8 pubmed publisher
    b>Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability...
  46. Nguyen G, Zhang S, Nguyen N, Nguyen P, Chiu M, 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. 2011;286:24275-87 pubmed publisher
    ..We show unambiguously that the cliotides are cyclotides and not A1bs, as determined by their sequence homology, disulfide connectivity, and membrane active properties ..
  47. Tang J, Wang C, Pan X, Yan H, Zeng G, Xu W, et al. Isolation and characterization of cytotoxic cyclotides from Viola tricolor. Peptides. 2010;31:1434-40 pubmed publisher
    Many plants of the Violaceae plant family have been used in traditional remedies, and these plants often contain cyclotides, a particular type of plant cyclopeptide that is distinguished by a cyclic cystine knot motif...
  48. Shenkarev Z, Nadezhdin K, Sobol V, Sobol A, Skjeldal L, Arseniev A. Conformation and mode of membrane interaction in cyclotides. Spatial structure of kalata B1 bound to a dodecylphosphocholine micelle. FEBS J. 2006;273:2658-72 pubmed
    b>Cyclotides are a family of bioactive plant peptides that are characterized by a circular protein backbone and three conserved tightly packed disulfide bonds...
  49. Gillon A, Saska I, Jennings C, Guarino R, Craik D, Anderson M. Biosynthesis of circular proteins in plants. Plant J. 2008;53:505-15 pubmed
    Plant cyclotides are a large family of naturally occurring circular proteins that are produced from linear precursors containing one, two or three cyclotide domains...
  50. Ireland D, Clark R, Daly N, Craik D. Isolation, sequencing, and structure-activity relationships of cyclotides. J Nat Prod. 2010;73:1610-22 pubmed publisher
    b>Cyclotides are a topologically fascinating family of miniproteins discovered over the past decade that have expanded the diversity of plant-derived natural products...
  51. Ireland D, Colgrave M, Nguyencong P, Daly N, Craik D. Discovery and characterization of a linear cyclotide from Viola odorata: implications for the processing of circular proteins. J Mol Biol. 2006;357:1522-35 pubmed
    b>Cyclotides are mini-proteins of 28-37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot...
  52. Thongyoo P, Bonomelli C, Leatherbarrow R, Tate E. Potent inhibitors of beta-tryptase and human leukocyte elastase based on the MCoTI-II scaffold. J Med Chem. 2009;52:6197-200 pubmed publisher
    MCoTI-II is a member of a class of microproteins known as cyclotides that possess a macrolactam-cystine knot scaffold imparting exceptional physiological stability and structural rigidity...
  53. Henriques S, Craik D. Cyclotides as templates in drug design. Drug Discov Today. 2010;15:57-64 pubmed publisher
    b>Cyclotides are remarkably stable proteins from plants that have a range of pharmaceutical and agricultural applications based on both their various bioactivities and their potential for use as stable protein-engineering templates...
  54. Aboye T, Ha H, Majumder S, Christ F, Debyser Z, Shekhtman A, et al. Design of a novel cyclotide-based CXCR4 antagonist with anti-human immunodeficiency virus (HIV)-1 activity. J Med Chem. 2012;55:10729-34 pubmed publisher
    ..This cyclotide also showed high stability in human serum, thereby providing a promising lead compound for the design of a novel type of peptide-based anticancer and anti-HIV-1 therapeutics. ..
  55. Dörnenburg H, Frickinger P, Seydel P. Plant cell-based processes for cyclotides production. J Biotechnol. 2008;135:123-6 pubmed publisher
    b>Cyclotides are naturally occurring mini-proteins that have a diverse range of therapeutically useful biological activities...
  56. Shenkarev Z, Nadezhdin K, Lyukmanova E, Sobol V, Skjeldal L, Arseniev A. Divalent cation coordination and mode of membrane interaction in cyclotides: NMR spatial structure of ternary complex Kalata B7/Mn2+/DPC micelle. J Inorg Biochem. 2008;102:1246-56 pubmed publisher
    The cyclotides are the family of hydrophobic bioactive plant peptides, characterized by a circular protein backbone and three knot forming disulfide bonds...
  57. Craik D. Host-defense activities of cyclotides. Toxins (Basel). 2012;4:139-56 pubmed publisher
    b>Cyclotides are plant mini-proteins whose natural function is thought to be to protect plants from pest or pathogens, particularly insect pests...
  58. Colgrave M, Kotze A, Kopp S, McCarthy J, Coleman G, Craik D. Anthelmintic activity of cyclotides: In vitro studies with canine and human hookworms. Acta Trop. 2009;109:163-6 pubmed publisher
    ..The cyclotides are a novel family of cyclic cystine knot containing peptides from plants that have been shown to possess ..
  59. Garcia A, Camarero J. Biological activities of natural and engineered cyclotides, a novel molecular scaffold for peptide-based therapeutics. Curr Mol Pharmacol. 2010;3:153-63 pubmed
    b>Cyclotides are a growing family of large plant-derived backbone-cyclized polypeptides (?30 amino acids long) that share a disulfide-stabilized core characterized by an unusual knotted structure...
  60. Ireland D, Colgrave M, Craik D. A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability. Biochem J. 2006;400:1-12 pubmed
    b>Cyclotides are a fascinating family of plant-derived peptides characterized by their head-to-tail cyclized backbone and knotted arrangement of three disulfide bonds...
  61. Dörnenburg H. Plant cell culture technology-harnessing a biological approach for competitive cyclotides production. Biotechnol Lett. 2008;30:1311-21 pubmed publisher
    b>Cyclotides are naturally occurring mini-proteins that have a cyclic backbone and a knotted arrangement of three disulfide bonds...
  62. Jennings C, Rosengren K, Daly N, Plan M, Stevens J, Scanlon M, 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 pubmed
    ..characterized and has a cis-peptidyl-proline bond, thus validating the suggested name for this subfamily of cyclotides. The observation that kalata B2 inhibits the growth and development of Helicoverpa armigera larvae suggests a ..
  63. Daly N, Craik D. Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1. J Biol Chem. 2000;275:19068-75 pubmed
    ..The cyclotides are the only naturally occurring family of circular proteins and have prompted us to explore the concept of ..
  64. Chen B, Colgrave M, Daly N, Rosengren K, Gustafson K, Craik D. 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 pubmed
    ..sequencing strategy featured by its efficiency, simplicity, and easy manipulation, the sequences of four novel cyclotides (macrocyclic knotted proteins) isolated from an Australian plant Viola hederaceae were determined...
  65. Nguyen G, Lian Y, Pang E, Nguyen P, Tran T, Tam J. 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 pubmed publisher
    b>Cyclotides are disulfide-rich macrocyclic peptides that display a wide range of bioactivities and represent an important group of plant defense peptide biologics. A few linear variants of cyclotides have recently been identified...
  66. Gruber C, Elliott A, Ireland D, Delprete P, Dessein S, Goransson U, et al. Distribution and evolution of circular miniproteins in flowering plants. Plant Cell. 2008;20:2471-83 pubmed publisher
    b>Cyclotides are disulfide-rich miniproteins with the unique structural features of a circular backbone and knotted arrangement of three conserved disulfide bonds...
  67. Saska I, Gillon A, Hatsugai N, Dietzgen R, Hara Nishimura I, Anderson M, et al. An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem. 2007;282:29721-8 pubmed
    ..The largest family of circular proteins are the plant-produced cyclotides; extremely stable proteins with applications as bioengineering scaffolds...
  68. Burman R, Herrmann A, Tran R, Kivelä J, 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 pubmed publisher
    The cyclotides are a family of circular and knotted proteins of natural origin with extreme enzymatic and thermal stability...
  69. Poth A, Colgrave M, Lyons R, Daly N, Craik D. Discovery of an unusual biosynthetic origin for circular proteins in legumes. Proc Natl Acad Sci U S A. 2011;108:10127-32 pubmed publisher
    b>Cyclotides are plant-derived proteins that have a unique cyclic cystine knot topology and are remarkably stable...
  70. Daly N, Clark R, Craik D. Disulfide folding pathways of cystine knot proteins. Tying the knot within the circular backbone of the cyclotides. J Biol Chem. 2003;278:6314-22 pubmed
    The plant cyclotides are a fascinating family of circular proteins that contain a cyclic cystine knot motif...
  71. Bokesch H, Pannell L, Cochran P, Sowder R, McKee T, Boyd M. A novel anti-HIV macrocyclic peptide from Palicourea condensata. J Nat Prod. 2001;64:249-50 pubmed
    ..Palicourein inhibits the in vitro cytopathic effects of HIV-1RF infection of CEM-SS cells with an EC50 value of 0.1 microM and an IC50 value of 1.5 microM. ..
  72. Craik D, Swedberg J, Mylne J, Cemazar M. Cyclotides as a basis for drug design. Expert Opin Drug Discov. 2012;7:179-94 pubmed publisher
    b>Cyclotides are plant-made defence proteins with a head-to-tail cyclic backbone combined with a conserved, six cystine knot...
  73. Hernandez J, Gagnon J, Chiche L, Nguyen T, Andrieu J, Heitz A, et al. Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure. Biochemistry. 2000;39:5722-30 pubmed
    ..MCoTIs represent interesting candidates for drug design, either by changing their specificity of inhibition or by using their structure as natural scaffolds bearing new binding activities. ..
  74. Hashempour H, Ghassempour A, Daly N, Spengler B, Römpp A. Analysis of cyclotides in Viola ignobilis by Nano liquid chromatography fourier transform mass spectrometry. Protein Pept Lett. 2011;18:747-52 pubmed
    b>Cyclotides are macrocyclic knotted peptides originating from plants. They are extremely stable and have a range of bioactivities including anti-HIV and insecticidal activity...
  75. Cemazar M, Daly N, Häggblad S, Lo K, Yulyaningsih E, Craik D. Knots in rings. The circular knotted protein Momordica cochinchinensis trypsin inhibitor-II folds via a stable two-disulfide intermediate. J Biol Chem. 2006;281:8224-32 pubmed
    ..The fact that macrocyclic proteins are readily able to fold to a complex knotted structure in vitro in the absence of chaperones makes them suitable as protein engineering scaffolds that have remarkable stability. ..
  76. Wang C, Wacklin H, Craik D. Cyclotides insert into lipid bilayers to form membrane pores and destabilize the membrane through hydrophobic and phosphoethanolamine-specific interactions. J Biol Chem. 2012;287:43884-98 pubmed publisher
    b>Cyclotides are a family of plant-derived circular proteins with potential therapeutic applications arising from their remarkable stability, broad sequence diversity, and range of bioactivities...
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    ..active components and their mechanisms, primarily focusing on uterotonic active circular plant peptides called cyclotides. Finally we will comment on the discovery of novel cyclotide-producing plant species and the possibility for the ..
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    ..Some of these peptides, included Kalata-peptide B1, have been shown to hold antimicrobial activity. They have recently been synthesized, and they may represent a starting point for the design of new peptide antibiotics. ..
  79. Wang C, Kaas Q, Chiche L, Craik D. CyBase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering. Nucleic Acids Res. 2008;36:D206-10 pubmed
    ..The new release of CyBase is available at http://research1t.imb.uq.edu.au/cybase. ..
  80. Goransson 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. 2004;5:317-29 pubmed
    This review focuses on the discovery of cyclotides in the Violaceae, their isolation and their anti-cancer effects...
  81. Gruber C, Cemazar M, Clark R, Horibe T, Renda R, Anderson M, et al. A novel plant protein-disulfide isomerase involved in the oxidative folding of cystine knot defense proteins. J Biol Chem. 2007;282:20435-46 pubmed
    ..Oldenlandia affinis (OaPDI), a coffee family (Rubiaceae) plant that accumulates knotted circular proteins called cyclotides. The novel plant PDI appears to be involved in the biosynthesis of cyclotides, since it co-expresses and ..