Background 



Alpha-amanitin is one of a group of fungal peptide 

 toxins isolated principally from members of the fungal 

 genus Amanita (Wieland, 1968). The structures of the 

 amanitins have been rigorously established as bicyclic 

 octapeptides containing two moles glycine, and one mole 

 each of hydroxytryptophan , cysteine, hydroxyproline , aspar- 

 agine (or aspartic acid) , isoleucine and a hydroxylated 

 isolencine, which varies depending on the derivative 

 (Wieland and Wieland, 1972; Fiume and Wieland, 1970; 

 Wieland and Faulstich, 1978). The sulfur atom of the cys- 

 teine residue is connected to the indol moiety of the tryp- 

 tophan ring via a sulfoxide bridge dividing the molecule 

 into two rings. Alpha-amanitin, the most common derivative, 

 contains asparagine and dihydroxyisoleucine and because 

 of its availability is the most thoroughly investigated of 

 the amanitins. 



The amanitins have been proven to possess extreme 

 toxicity for mammalian cells, in vitro and in vivo (Wieland 

 and Wieland, 1959; Fiume and Wieland, 1970; Sekeris and 

 Schmidt, 1972). Amanitins derive their toxicity from the 

 ability of the toxins to bind with high affinity to eucary- 

 otic DNA-directed RNA polymerase II (Stirpe and Fiume, 1967; 

 Seifart and Sekeris, 1969; Lindell at al. , 1970; Jacob et 

 al., 1970). The specificity and high affinity of the inter- 

 action of amanitins with polymerase is reflected by the 



