BARBARA W. LOW AND JOHN T. EDSALL 



loop. This loop, which involves a 20-atom ring, closed by the 

 disulfide bond, has also been found by du Vigneaud and his 

 associates (106,107) in the very different structures of the 

 smaller polypeptide hormones, oxytocin and vasopressin, with 

 different sets of amino acid residues in the loop. Here, in the 

 case of oxytocin at least, the structure has been completely 

 proved by synthesis. The presence of this unusual ring (Figure 2) 



X— NH-CH-CHp-S— S-CHp-CH-CO— Y- 



I I 



CO NH 



I I 



NH CO 



I I 



R|-GH CH-R4 



CO NH 



I I 



NH-CH-CO-NH-CH-CO 



Fig. 2. The peptide-disulfide ring structure of oxytocin, vasopressin, and 

 insulin. The attached groups at positions X, Y, Ri, R2, R3, and R4 are indi- 

 cated below. 



in several different protein or peptide hormones is a striking 

 phenomenon ; one cannot help suspecting that it bears a special 

 relation to the physiological activities of these compounds. Yet 

 it is remarkable that the only differences between the three 

 insulins are found among the amino acid residues in this ring; 

 a single unique set of side chains here is clearly not required for 

 the physiological activity of insulin. Moreover there is no reason 

 to suppose that the spatial configuration of this 20-atom ring 

 is at all the same, in insulin, oxytocin, and vasopressin; indeed 

 the presence of the adjoining disulfide link to the B chain at 



380 



