SECTION IV 

 DISCUSSION 



The primary objectives of this investigation were to 

 assess the effectiveness of certain macromolecules , 

 Concanavalin A in particular, to impart selectivity with 

 respect to cellular uptake to the fungal toxin a-amanitin, 

 and to evaluate the ability of cell surface receptors to 

 mediate the entry of macromolecule bound toxin into the 

 cell and thus specifically kill that cell. Achievement of 

 these objectives required that a system be developed by 

 which conjugates of a-amanitin and carrier macromolecules 

 could be synthesized, characterized for retention of a- 

 amanitin and carrier associated properties and evaluated 

 for specificity of interaction with selected mammalian 

 cells. The initial phase of this development was stimula- 

 ted by the investigations of Fiume and coworkers with con- 

 jugates of B-amanitin and proteins (Cessi and Fiume, 1969; 

 Fiume et al., 1969; Fiume et al., 1971; Barbanti-Brodano 

 and Fiume, 1974; Fiume and Barbanti-Brodano, 1974). 



ADH-BSA Conjugates 



The work described here utilized the most widely 

 occurring derivative of the amatoxins, a-amanitin, which is 

 available in quantity from locally gathered specimens. The 



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