STRUCTURE OF INSULIN 



in Figure 5, which has a molecular weight of 12,000, would 

 also fit our experimental results. However, it is most im- 

 probable that such a molecule with two disulfide bonds joining 

 the two identical halves would dissociate under the conditions 

 used by Harfenist and Craig to demonstrate a molecular weight 

 of 6000. 



The structure given embodies a disulfide ring joining the 

 two CyS residues in positions A6 and All. This ring is the 

 same size as the disulfide rings found in oxytocin (26,27) and 

 vasopressin (1,28). The three hormones have very different 

 biological functions, but the presence of this common structure 



Phe.- 

 Gly.- 



-1 '■ r" Gly. 



I I 

 -i ' -Phe. 



Figure 5. 



may have some physiological significance and may be reflected 

 in a mechanism that is common to these polypeptide hormones. 

 The ring disulfide does not show any particular chemical re- 

 activity in vitro and appears to be more stable to reduction and in 

 the disulfide interchange reaction than are cystine or oxidized 

 glutathione. Nothing, however, is known about its reactivity 

 in vivo. 



To form the disulfide ring the polypeptide chain must be 

 oriented in such a way that the two CyS residues are close to- 

 gether. This imposes definite limitations on the various con- 

 figurations that can be considered for this part of the chain. 

 The popular a-helix with 3.7 residues per turn can clearly not be 

 present here, and it will be interesting to see what other struc- 

 tures are possible. The stability of the ring and the fact that 

 reduced oxytocin can be readily converted to the disulfide ring 

 form by oxidation suggest that no great distortion of the stable 

 configuration of the polypeptide chain is brought about by for- 

 mation of the disulfide bond. 



455 



