Cyclotide Sequences

What are Cyclotides?
Uses of Cyclotides
About Us
Discovery of Cyclotides
Biological Activity
Topological Features
Cyclotide Genes
Cystine Knots
Other Circular Proteins
Cybase: The Cyclotide Database
Commercial Opportunities
Contact Us

Moebius cyclotides are so named because they contain a conceptual twist in their backbone. Further investigate moebius strips at

M.C. Escher used Moebius strips in his work. Eschers artwork can be investigated at the Cordon Art B.V. web site.
Table One: Discovered cyclotides and their sequences.
The cyclotides can be divided into two families based on whether they possess a conceptual twist caused by a cis-Pro peptide bond in loop 5. Cyclotides possessing a twist are classified as Moebius and those lacking the cis-Pro bond are Bracelet cyclotides. The trypsin inhibitor cyclotides are classfied in their own family based on sequence variation and natural activity. The X in Violapeptide I was not determined in the original report but is presumably R based on sequence homology.
See larger view of table in a pop-up window

Table 1 has been split into sub-families, based on the classification of the backbone as either of Möebius or Bracelet type (Craik, et al., 1999). This nomenclature arises because it has been proposed that a cis-Pro peptide bond in loop 5 can be thought of as providing a twist in the conceptual ribbon of the peptide backbone, leading to the circular backbone being regarded as a Möebius strip. When this cis-Pro is not present, all backbone peptide bonds are in the trans arrangement, making the backbone bracelet-like. Hence, the cyclotide family is divided based on the presence (or absence) of the putative cis-Pro peptide bond in loop 5. It is stressed that this is a convenient conceptual description only and it is not suggested that the molecules exhibit the topological properties of either bracelets or Möebius strips.

Figure One also summarises the conserved and variable residues of the cyclotides: the six conserved cysteine residues are in yellow, other conserved residue in green and variable residues in blue (Craik, et al., 1999).

Figure One: Schematic of a cyclotide showing conserved residues (green), cysteine residues (yellow) and variable residues (blue) along with the three dimensional structure of cycloviolacin O1.


Bokesch HR, Pannell LK, Cochran PK, Sowder RC, 2nd, McKee TC and Boyd MR: A novel anti-HIV macrocyclic peptide from Palicourea condensata. J. Nat. Prod. (2001) 64:249-250.

Broussalis AM, Goransson U, Coussio JD, Ferraro G, Martino V and Claeson P: First cyclotide from Hybanthus (Violaceae). Phytochemistry (2001) 58:47-51.

Claeson P, Göransson U, Johansson S, Luijendijk T and Bohlin L: Fractionation protocol for the isolation of polypeptides from plant biomass. J. Nat. Prod. (1998) 61:77-81.

Craik DJ, Daly NL, Bond T and Waine C: Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J. Mol. Biol. (1999) 294:1327-1336.

Göransson U, Luijendijk T, Johansson S, Bohlin L and Claeson P: Seven novel macrocyclic polypeptides from Viola arvensis. J. Nat. Prod. (1999) 62:283-286.

Gustafson KR, Sowder II RC, Henderson LE, Parsons IC, Kashman Y, Cardellina II JH, McMahon JB, Buckheit Jr. RW, Pannell LK and Boyd MR: Circulins A and B: Novel HIV-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia. J. Am. Chem. Soc. (1994) 116:9337-9338.

Hallock YF, Sowder RCI, Pannell LK, Hughes CB, Johnson DG, Gulakowski R, Cardellina JHI and Boyd MR: Cycloviolins A-D, anti-HIV macrocyclic peptides from Leonia cymosa. J. Org. Chem. (2000) 65:124-128.

Hernandez JF, Gagnon J, Chiche L, Nguyen TM, Andrieu JP, Heitz A, Trinh Hong T, Pham TT and Le Nguyen D: Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure. Biochemistry (2000) 39:5722-5730.

Jennings C, West J, Waine C, Craik D and Anderson M: Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affinis. Proc. Natl. Acad. Sci. U. S. A. (2001) 98:10614-10619.

Schöpke T, Hasan Agha MI, Kraft R, Otto A and Hiller K: Hämolytisch aktive komponenten aus Viola tricolor L. und Viola arvensis Murray. Sci. Pharm. (1993) 61:145-153.

Witherup KM, Bogusky MJ, Anderson PS, Ramjit H, Ransom RW, Wood T and Sardana M: Cyclopsychotride A, A biologically active, 31-residue cyclic peptide isolated from Psychotria Longipes. J. Nat. Prod. (1994) 57:1619-1625.