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First cyclotide from Hybanthus (Violaceae)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2001 (English)In: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 58, no 1, 47-51 p.Article in journal (Refereed) Published
Abstract [en]

Hypa A, a novel macrocyclic polypeptide containing 30 amino acid residues, has been isolated from the n-butanol extract of the Argentine plant Hybanthus parviflorus. The sequence, cyclo-(SCVYIPCTITALLGCSCKNKVCYNGIPCAE), was determined by automated Edman degradation, quantitative amino acid analysis and nanospray MS/MS(2). Three intramolecular disulfide bridges stabilize the cyclic peptide backbone of hypa A. Using these structural features to classify the peptide as a cyclotide, we extended the distribution of that substance class to a new genus, and now propose a uniform nomenclature for cyclotides.

Place, publisher, year, edition, pages
2001. Vol. 58, no 1, 47-51 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-89793DOI: 10.1016/S0031-9422(01)00173-XPubMedID: 11524112OAI: oai:DiVA.org:uu-89793DiVA: diva2:161547
Available from: 2002-04-05 Created: 2002-04-05 Last updated: 2012-01-24Bibliographically approved
In thesis
1. Macrocyclic polypeptides from plants
Open this publication in new window or tab >>Macrocyclic polypeptides from plants
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this work was to explore the structural and functional diversity of polypeptides that are found in plants. Expanding knowledge of simililarities between plant use of these compound and animal use promises exceptional opportunities for finding, from plant research, new structures with biomedical and biotechnological potential.

A fractionation protocol was developed and applied to many plant species, providing fractions enriched in polypeptides, amenable to chemical and biological evaluation. From one species, the common field pansy (Viola arvensis), a 29-amino-acid residue polypeptide was isolated, named varv A, which revealed a remarkable macrocyclic structure (i.e., N- and C-termini are joined) stabilised by three knotted disulfides.

Varv A, together with an increasing number of homologous peptides, form the currently known peptide family of cyclotides. Their stable structure makes them an attractive scaffold for protein engineering. In addition, they display a wide range of biological activities (e.g., antimicrobial, cytotoxic, and insecticidal). As a part of this work, the cytotoxic effects of varv A and two other isolated cyclotides were evaluated in a human cell-line panel: all were active in the low µM range. Most likely, these effects involve pore formation through cell membranes.

Cyclotides were found to be common in the plant family Violaceae; with eleven cyclotides isolated and sequenced from V. arvensis, V. cotyledon, and Hybanthus parviflorus. For six members of the genus Viola, cyclotide expression profiles were examined by liquid chromatography-mass spectrometry (LC-MS): all expressed notably complex mixtures, with single species containing more than 50 cyclotides. These profiles reflect the evolution of the genus.

To assess these mixtures, a rational strategy for MS based amino acid sequencing of cyclotides was developed, circumventing inherent structural problems, such as low content of positively charged amino acids and the macrocyclic structure. This was achieved by aminoethylation of cysteines, which, following tryptic digestion, produced fragments of size and charge amenable to MS analysis. This method was also modified and used for mapping of disulfide bonds.

Methods for isolation and characterisation developed in this work may prove useful not only for further studies on macrocyclic polypeptides from plants, but also for other plant peptides and disulfide-rich peptides from animals.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 59 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 270
Pharmaceutical chemistry, Farmaceutisk kemi
National Category
Medicinal Chemistry
Research subject
urn:nbn:se:uu:diva-1956 (URN)91-554-5279-5 (ISBN)
Public defence
2002-04-26, BMC sal B22, Uppsala, 10:15
Available from: 2002-04-05 Created: 2002-04-05 Last updated: 2013-06-10Bibliographically approved

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