The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity

Herrman, Anders, Burman, Robert, Mylne, Joshua S., Karlsson, Gustav, Gullbo, Joachim, Craik, David J., Clark, Richard J. and Goransson, Ulf (2008) The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity. Phytochemistry, 69 4: 939-952. doi:10.1016/j.phytochem.2007.10.023


Author Herrman, Anders
Burman, Robert
Mylne, Joshua S.
Karlsson, Gustav
Gullbo, Joachim
Craik, David J.
Clark, Richard J.
Goransson, Ulf
Title The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity
Formatted title
The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity
Journal name Phytochemistry   Check publisher's open access policy
ISSN 0031-9422
Publication date 2008-02-01
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.phytochem.2007.10.023
Open Access Status
Volume 69
Issue 4
Start page 939
End page 952
Total pages 14
Editor G. P. Bolwell
Place of publication New York , U.S.A.
Publisher Elsevier
Language eng
Subject C1
250399 Organic Chemistry not elsewhere classified
970103 Expanding Knowledge in the Chemical Sciences
060702 Plant Cell and Molecular Biology
Abstract The cyclotides are currently the largest known family of head-to-tail cyclic proteins. The complex structure of these small plant proteins, which consist of approximately 30 amino acid residues, contains both a circular peptide backbone and a cystine knot, the combination of which produces the cyclic cystine knot motif. To date, cyclotides have been found in plants from the Rubiaceae, Violaceace and Cucurbitaceae families, and are believed to be part of the host defence system. In addition to their insecticidal effect, cyclotides have also been shown to be cytotoxic, anti-HIV, antimicrobial and haemolytic agents. In this study, we show that the alpine violet Viola biflora (Violaceae) is a rich source of cyclotides. The sequences of 11 cyclotides, vibi A-K, were determined by isolation and MS/MS sequencing of proteins and screening of a cDNA library of V. biflora in parallel. For the cDNA screening, a degenerate primer against a conserved (AAFALPA) motif in the cyclotide precursor ER signal sequence yielded a series of predicted cyclotide sequences that were correlated to those of the isolated proteins. There was an apparent discrepancy between the results of the two strategies as only one of the isolated proteins could be identified as a cDNA clone. Finally, to correlate amino acid sequence to cytotoxic potency, vibi D, E, G and H were analysed using a fluorometric microculture cytotoxicity assay using a lymphoma cell line. The IC50-values of the bracelet cyclotides vibi E, G and H ranged between 0.96 and 5.0 μM while the Möbius cyclotide vibi D was not cytotoxic at 30 μM.
Keyword Viola biflora L.
Violaceae
Arctic yellow-violet
Two-flower violet
Cyclotides
Circular proteins
cDNA screening
Cytotoxicity
MS/MS
Anticancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: 2009 Higher Education Research Data Collection
 
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Created: Wed, 15 Apr 2009, 21:43:40 EST by Jennifer Greder on behalf of Institute for Molecular Bioscience