SECTION I 

 INTRODUCTION 



Objectives 



The overall objectives of this research were to assess 

 the potential of selected proteins for targeting of inhi- 

 bitors to specific cells and to evaluate the ability of 

 cell membrane receptors to mediate uptake of these protein- 

 inhibitor conjugates. The specific objectives defined for 

 accomplishing this were: 1) synthesis and biochemical 

 characterization of conjugates of a-amanitin and bovine 

 serum albumin (BSA) and concanavalin A (Con A) , 2) deter- 

 mination of the degree to which Con A conjugates retain the 

 biological properties of each component of the conjugate, 

 and 3) the use of a-amanitin-Con A conjugates to investi- 

 gate the effectiveness of Con A as a targeting vehicle 

 for a-amanitin based on the numbers and/or affinities of 

 Con A receptor sites present on the target cell. The 

 effectiveness of Con A for imparting selectivity with 

 respect to cellular uptake to a-amanitin and the ability 

 of cell surface receptors to mediate the entry of bound 

 toxin and thereby be specifically killed, were used as 

 criteria for assessing the degree to which these objec- 

 tives were fulfilled. 



