Viscum album L. contains a group of amphipathic, strongly basic polypeptides, named viscotoxins. At least six isomeric viscotoxins were isolated by Samuelsson (1974) and Urech et al. (1995), mainly from Viscum album species. These peptidetoxins are strongly related to an already known group of amphiphilic basic peptides, thionins, which share a rather similar structure of 46 amino acids. They are common in plants like corn, wheat and others, and are suggested to be protective substances against infections by viruses, bacteria and fungi (Carrasco et al., 1981).
Viscotoxins have a molecular weight of about 5 kD (isoelectric points at pH 9-11) and contain 3 to 4 disulphide bridges. The amino acid sequences of the most important of them, viscotoxin A2, A3, B, were published by Samuelsson (1974). Beside the sequence data, a molecular model of the viscotoxin A3 is given by Barre et al. (1996, 1997). The three-dimensional-models of viscotoxin A3 and of alpha 1-purothionin (from Durum wheat) revealed that both polypeptides are amphipathic, and thus may interact with membrane lipid bilayers. The viscotoxins as well as other thionins are very stable polypeptides even under denaturating conditions and tend to self-aggregate and to form protein-lipid-complexes, even soluble in simple hydrocarbons (Fernandez de Caleya et al., 1974).
The physico-chemical properties of the membrane-permeabilising viscotoxins (Büssing et al., 1999a, b) may explain some of their biological and pharmacological activities. However, it is unclear why amphipathic polypetides from mistletoe and other plants sharing great extend of structural identity show quite different biological behaviour. One may suggest that a change of only few amino acids in the biologically less active thionins may change the cytotoxic potential of the polypeptides, as suggested for viscotoxin B as compared to viscotoxin A2 (Büssing et al., 1999a). Therefore, the amphipathic properties, more or less equal in the studied polypeptides, must be completed by other structural features resulting in the comparable high solubility in water and outstanding biological activities of the viscotoxins.
Due to their tendency to form complexes with ML, the viscotoxins may modulate the interactions of ML with carbohydrates. One of the three disulphide bridges in the viscotoxins is well exposed and may thus be involved in SS/SH-exchange reactions with ML forming a covalent bond between both (Pfüller, unpublished observations).
Due to their outstanding properties and the occurrence in many commercially available mistletoe preparations, the viscotoxins are candidates for further investigations on the action of mistletoe extracts to the human organism (Stein et al. 1999a, b). On the other hand, the behaviour and modulating ability of thionins, widely distributed in food and feed, should be carefully discussed in regard of their potential impact for nutrition and therapy.
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