Mutagenic Alkylating Agents 



297 



every case the agent was present in great excess. Very little 

 is known of the combination of the other types of radiomimetic 

 alkylating agents with proteins and this led us to examine 

 systematically the reaction of a representative number of 

 these with serum albumin under physiological conditions. 

 The reaction with the different groups in the intact proteins 

 was determined by a variety of methods (Cousens, 1956). The 

 results, summarized in Table I, indicate that the most pro- 

 minent reaction common to all the biologically active alkylat- 



Table I 



Changes Produced in Serum Albumin by Radiomimetic 

 Agents 



Treatment 



0=rCH2CH— CH2I 



\ / 



CH3 • CH — CHo 



Myleran 

 Chlorambucil 



Protein Solution + 0-12 Moles of Reagent 



ing agents is esterification of the carboxyl groups. The 

 epoxides reacted extensively with amino groups of lysine 

 and the imino group of histidine; the nitrogen mustards 

 reacted to a lesser extent and the mesyloxy compounds hardly 

 at all. 



Chromatographic examination of the acid hydrolysate of 

 the reacted proteins showed an almost complete disappear- 

 ance of the spot due to histidine after reaction with epoxides 

 and a very noticeable decrease after treatment with nitrogen 

 mustard. The intensity of the lysine spot was also changed. 



