15 



chemical nature that retain inhibitory potential for RNA 

 polymerase II. 



For targeting of a-amanitin to specific cell receptors 

 Con A will be used. Con A is well characterized chemically 

 and, unlike specific immunoglobulins, is available in quan- 

 tity from commercial sources. The conjugation with a-ama- 

 nitin can be monitored by a number of biochemical and bio- 

 logical parameters for its effects on lectin activity. 

 Specific ligands with known binding affinities for Con A 

 are available, as are defined systems for evaluating the 

 interaction of Con A conjugates with cells. 



Following synthesis and characterization of the a- 

 amanitin-Con A conjugates, the final aspect of the study 

 will be to evaluate the potential of Con A for targeting 

 a-amanitin to cells and the ability of Con A receptors to 

 mediate uptake of bound conjugate. Although it would 

 appear that the differences in Con A binding between normal 

 and virally transformed cells would represent a potential 

 system for discerning targeting differences of Con A con- 

 jugates, the conditions necessary to achieve quantitative 

 differences in the number of cell receptors and the low 

 magnitude of the observed differences, suggest other 

 approaches may be more productive. A cell line known 

 to possess a distinct number of Con A receptors, H-7 CHO , 

 will be used to examine the cytotoxicity of Con A-a-amanitin 

 conjugate in comparison to free a-amanitin. The study will 

 be restricted to evaluating whether specific interaction 



