312 CHOH HAO LI [18 



it may be inferred that those portions of the molecule containing 

 these differences are not essential for biological potency. Indeed, limited 

 hydrolysis of both corticotropins with pepsin releases 11 amino acid resi- 

 dues from the C-terminus without loss of adrenal-stimulating activity. '*^'*^'^^''*^ 

 Further hydrolysis of this active core with dilute acid did not result in any 

 loss of ACTH activity.^'' Recently, the synthesis of the first 20 amino acids 

 from the A^-terminus of the corticotropins has been achieved by Boissonnas 



Table 4 



VARIATIONS IN AMINO ACID SEQUENCES AMONG DIFFERENT 

 PREPARATIONS OF ACTH 



et al.,^'^ and the synthetic icosapeptide has been demonstrated to possess 

 ACTH activity. Thus, both the sheep and pig corticotropins appear to have 

 an identical active core that is responsible for their hormonal function. 



The behavior of corticotropin-A and a-corticotropin in countercurrent 

 distribution reveals marked differences in the partition coefficients of these 

 peptides in various solvent systems. For example, the partition coefficient 

 of corticotropin-A in a 2-butanol/0-2% TCA system is 1-82,^^ whereas that 

 of a-corticotropin in the same system is O-Tl."*^ In a solvent system made 

 up of 6% acetic acid containing 3-5% NaCl/«-BuOH, corticotropin-A (Cyan- 

 amid) has a K value of 0-95,^^ whereas that of a-corticotropin in the same 

 system is less than O-l.*^ It is unhkely that these differences are due to 

 variation in amide content among the various corticotropin preparations, 

 since, even though there is a difference of 2 amide groups between two 

 preparations of a-corticotropin, they cannot be differentiated by their be- 

 havior in countercurrent distribution in a 2-butanol-aqueous TCA system.*^ 



There are also some indications that corticotropin-A and a-corticotropin 

 may be distinguished from each other according to their behavior in enzy- 

 matic hydrolysis. The peptide fragment Lys.Arg.Arg.Pro.Val.Lys occurs in 

 the tryptic digest of corticotropin-A (Cyanamid)*^ but it is not encountered 

 in similar digests of a-corticotropin.^^ Moreover, the sheep hormone appears 

 to be more labile toward pepsin than is the pig hormone. It is not improb- 

 able that two polypeptides possessing similar amino acid sequences may 

 differ in the spatial arrangement (helices) of the residues which compose it, 



