Heptapeptide phallotoxins

Synthetic peptides containing side-chain modification have also been used as molecular scaffolds for the preparation of multiple receptors and molecular devices. 5 These include the use of crown ethers, cyclodextrins, porphyrins, and peptides with metal-binding sites (including ferrocenyl and EDTA side chains) (Section 9.4). Cyclization procedures have been developed to prepare biologically active cycloisodityrosine peptides which contain 14-or 17-membered rings (Section 9.5). The use of tryptathionine, a cross-linking dipeptide consisting of side-chain-to-side-chain linked L-Trp-L-Cys that is present in phallotoxins, 6 a family of cyclic heptapeptides, is also described (Section 9.6). 

The poisonous components of the most deadly mushroom Amanita phalloides (the Death Cap) are bicyclic heptapeptides which have an additional covalent bond that connects the ( -sulfur atom of an l-cysteine residue with the carbon atom in position 2 of the indole ring of the L-tryptophan. Phalloidin (or phalloidine) is the most abundant member of a whole family of related cyclic heptapeptides called phallotoxins (for a review, see Wieland1 1). These poisonous peptides, therefore, contain a cross-linking moiety consisting of L-tryptophan coupled to L-cysteine, designated tryptathionine (1), alternatively called 5-(trypto-phan-2-yl)cysteine or 2-(L-3-alanylsulfenyl)-L-tryptophan (Scheme 1). 

Another model phallotoxin 7 can be prepared from heptapeptide 6. Dissolving heptapepide 6 in TFA leads to the removal of both TV-Boc and. S -Trt protecting groups and concomitant cyclization to form the tryptathionine moiety. 13 A second cyclization of the monocyclic... 

From a chemical point of view amatoxins and phallotoxins are bicyclic octapeptides and heptapeptides, respectively, whereas virotoxins are monocyclic heptapeptides (Figs. 7-9). All contain the indole nucleus of a... 

The extremely poisonous green mushroom Amanita phalloides contains a number of cyclic peptides classified as phallotoxins (heptapeptides), ama-toxins (octapeptides), and a decapeptide antagonist called antamanide (Wieland and Wieland, 1972). Crystal structure analyses have been completed on jS-amanitin, on antamanide, and on a biologically active analog, both com-plexed and uncomplexed. 

Virotoxins. A group of monocyclic heptapeptides from the toadstool Amanita vimsa (destroying angel). Together with the amanitins and phallotoxins, they represent the third class of poisons in death caps. Six compounds are known viroisin is the main toxin. 

Phallotoxins heterodetic, cyclic heptapeptides, present in Amanita phalloides. Together with the Amatoxins (see), P. are the main toxic components of this fungus. The chief P. are phalloidin, phalloin and phallacidin (Fig.). Phallacidin is similar to phalloidin, but the D-threonine-alanine grouping is replaced by valyl-D-erythro-P-hydroxyaspartic acid. P. are not as toxic as the amatoxins, but they act more quickly. The structural requirements for toxicity... 

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