Abstract
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. The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling. They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity. There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years. Ultimately the family may comprise thousands of members. This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries. Their unique topological features make them interesting from a protein folding perspective. Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection.
Keywords: cyclotides, disulfide rich proteins, cyclic peptide backbone, uterotonic action, anti-HIV activity, neurotensin antagonism, insecticidal activity
Current Protein & Peptide Science
Title: Discovery, Structure and Biological Activities of the Cyclotides
Volume: 5 Issue: 5
Author(s): David J. Craik, Norelle L. Daly, Jason Mulvenna, Manuel R. Plan and Manuela Trabi
Affiliation:
Keywords: cyclotides, disulfide rich proteins, cyclic peptide backbone, uterotonic action, anti-HIV activity, neurotensin antagonism, insecticidal activity
Abstract: 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. The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling. They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaceae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity. There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years. Ultimately the family may comprise thousands of members. This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries. Their unique topological features make them interesting from a protein folding perspective. Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection.
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Cite this article as:
Craik J. David, Daly L. Norelle, Mulvenna Jason, Plan R. Manuel and Trabi Manuela, Discovery, Structure and Biological Activities of the Cyclotides, Current Protein & Peptide Science 2004; 5 (5) . https://dx.doi.org/10.2174/1389203043379512
DOI https://dx.doi.org/10.2174/1389203043379512 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
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