58 CHARLES TANFORD [3 



albumin, so that the changes indicated by Fig. 14 represent behavior which 

 is much more nearly symmetrical about the isoelectric point. 



It should be noted that the expanded configurations of all of the proteins 

 discussed above, though they behave qualitatively like simple polyelectro- 

 lytes, do not have intrinsic viscosities as large as those of simple poly- 

 electrolytes of similar molecular weight and charge. This result is to be expected, 

 as has been mentioned, because disulfide cross-links limit the expansion which 



Mo 



--80^ 



- -70' 



■60 



- -50 



10 12 



pH 



Fig. 14. Intrinsic viscosity (0) and specific rotation (Q) of y-globulin at ionic strength 

 0-1 (Jirgensons*"). This protein is a mixture of components with different isoelectric points, 

 the average of which is near pH 7. 



protein molecules can undergo. It is important to point out, in addition, 

 that it is virtually impossible to distinguish configurations consisting of a 

 mixture of compact and randomly coiled parts from a configuration which 

 is completely random except for cross-links. In other words, though the 

 measurements cited clearly show polyelectrolyte-like properties, this does 

 not yet provide a complete picture of the expanded configurations. 



We shall list next, some globular proteins which are much more resistant 

 to configurational change than those discussed above. 



Ribonuclease. In contrast to the proteins just discussed, ribonuclease is highly 

 resistant to configurational change. As Fig. 7 shows, its intrinsic viscosity 

 is virtually independent of charge and ionic strength between pH 1 and 

 pH 11-5.^" At pH 11-5, there is a configurational change which brings three 

 phenolic groups from the interior of the molecule to the surface.^^ Whether 

 this reaction also leads to expansion is not known. At pH 1-0 and ionic 



