88 IMMUNO-CATALYSIS 



necessity of invoking also a variation in the amino-acid composition 

 or amino-acid order." 



A globulin molecule is pictured as consisting of a single polypeptide 

 chain, containing several hundred amino-acid residues. The arrange- 

 ment of the amino-acid residues in the central part is much more 

 stable than any other, whereas the two end parts of the chain are of 

 such a nature that there exist for them many configurations with 

 nearly the same energy. "The atoms and groups which form the sur- 

 face of the antigen will attract certain complementary parts of the 

 globulin chain (a negatively-charged group, for example, attracting 

 a positively-charged group), and repel other parts. As a result of these 

 interactions the configurations of the chain ends which are stable in 

 the presence of the antigen will be such that there is attraction between 

 the coiled globulin chain ends and the antigen, due to their com- 

 plementarity in structure. The configuration assumed by the chain end 

 may be any one of a large number, depending upon which part of 

 the surface of the antigen happens to exert its influence on the chain 

 end and how large a region of the surface happens to be covered by 

 it." The middle part of the antibody molecule thus produced would 

 be like that of a normal globulin molecule. Hence antibodies should 

 have antigenic activity, with essentially complete cross reactions with 

 normal globulin. The two ends, on the other hand, would have con- 

 figurations more or less complementary to parts of the surface of the 

 antigen. According to this picture the active end regions of the anti- 

 body molecule would not have effective antigenic power.* This is 

 explained by assuming that the configurations of the end regions 

 would be different from molecule to molecule, and that an antibody 

 complementary to one antibody end would as a rule not combine with 

 another. 



*The concept of Pauling appears to be in contradiction to the results provided by 

 the studies of Northrop (1942). He reported that diphtheria antitoxin (mol. wt. 

 184,000) on digestion with proteolytic enzymes was obtainable in crystalline form. 

 This substance was 90 per cent precipitable with diphtheria toxin and had a molec- 

 ular weight of 90,000. The immune sera prepared against the crystalline substance 

 were active against antitoxin but inactive against the normal serum proteins. 



The fact that the crystalline substance represents one-half of the original antitoxin 

 molecule, fails to support the hypothesis of Pauling that the antibody molecule is 

 made up of a stable midpiece carrying at each end polypeptide chains susceptible 

 to configurational changes. In view of Northrop's results it would seem difficult to 

 label certain parts of the antibody molecule as corresponding to mid or end pieces. 



