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Comparison of extraction methods for alkaline thionins from mistletoes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Pharmacognosy.
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2012 (English)Article in journal (Refereed) Submitted
Place, publisher, year, edition, pages
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95569OAI: oai:DiVA.org:uu-95569DiVA: diva2:169841
Available from: 2007-03-09 Created: 2007-03-09 Last updated: 2012-03-22Bibliographically approved
In thesis
1. Mistletoes and Thionins: as Selection Models in Natural Products Drug Discovery
Open this publication in new window or tab >>Mistletoes and Thionins: as Selection Models in Natural Products Drug Discovery
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The process of drug discovery from natural products starts with the selection of study object. In this project recent knowledge and methods are incorporated to investigate the process of such selection for pharmacognostic investigations. As the model and object of study mistletoes and their content of the small cytotoxic peptides thionins are chosen.

The thionins are compared in silico to other proposed plant innate defense peptides. Utilizing analysis of amino acid sequences and secondary structures, the thionins are shown to be one of eight distinct groups of cystein-rich plant polypeptides analysed. Common features of thionins are exploited in an investigation of isolation methods, where a simple acidic extraction is equally efficient to isolate thionins as the laborious methods hitherto used.

An effort to study the relationships of the order Santalales was done. To infer phylogenetic relationships from DNA sequences, we increased the taxon sampling for utilized genes and regions such as rbcL, atpB and ribosomal 18S and 26S rDNA sequences within the Santalales. Analysing these together with published sequences for other tricolpate taxa a position for Santalales as sister to caryophyllids and basal to asterids is implied. This indication is supported by chemical characters such as the presence of cyclopeptide alkaloids of a kind only known from Gentianales.

To validate the chemosystematic implications from thionin distribution extracts of mistletoes collected in Panama, Taiwan and Madagascar, and the relative Osyris alba (Santalaceae) collected in Spain, were screened with the established fluorescence microculture cytotoxicity assay using the thionin-sensitive human lymphoma cell-line U937GTB. Bioassay guided isolation concludes that the cytotoxic compounds in Loranthaceae may however constitute another group of peptides.

In conclusion this work shows that the incorporation of informatic techniques may aid prediction and decision making when planning pharmacognostic research.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 49
Pharmacognosy, drug discovery, mistletoe, phylogeny, cytotoxic peptides, Santalales, Farmakognosi
urn:nbn:se:uu:diva-7705 (URN)978-91-554-6824-8 (ISBN)
Public defence
2007-03-30, B41, BMC, Uppsala, 13:00
Available from: 2007-03-09 Created: 2007-03-09Bibliographically approved

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Backlund, Anders
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