■â ä ' â à^ -^ # ':cf " «*' 4' ' i^ ■' f ' il^ 'Va*' ^'^ 



•# ij^ '^^ 



18] STRUCTURE OF MSH AND ACTH PEPTIDES 335 



serine, occurs as an jV-substituted derivative, whilst the C-terminal residue, 

 vahne, occurs as the amide. The TV-terminal moiety in a-MSH has been 

 provisionally identified as TV-acetylserine, but additional confirmatory ex- 

 periments are still in progress.* The presence of these additional substituents 

 provides an explanation, both for its highly basic iso-electric point and for 

 its unexpected solubility in acetone (Lee and Lerner, 1956). 



STRUCTURAL AND ACTIVITY RELATIONSHIPS 



BETWEEN THE a- AND jS-MELANOCYTE 



STIMULATING HORMONES AND THE 



CORTICOTROPINS 



The amino acid sequences of the two melanocyte-stimulating hormones, 

 together with the related A^-terminal segment of the corticotropins, are illus- 

 trated in Fig. 3. The heptapeptide, Met.Glu.His.Phe.Arg.Try.Gly, is common 



4 5 6 7 8 9 IG 

 M2t.Glu.Hls.Phe.Arq.Try. Gly. 



4 S 6 7 8 9 10 

 Mci.GluHis.Phe.Arg. Try. Gly 



7 8 9 ID II 12 13 

 M«t.Glu.Hls.Phe. Arg. Try Gly 



IS 

 Pro. 



- 1 

 13 I 14 

 Val.iGly--- 



I 



I 



13 1 

 Val|-NHa 



39 

 Phe — OH 



16 17 18 

 PrûLys. Asp- OH 



Fig. 3. Amino-acid sequences of the a, and j3-melanocyte-stimulating hormones, and 

 the related TV-terminal segment of corticotropin, from pig pituitary glands. 



to all three molecules, and it is only the interchange of lysine and serine 

 residues (positions 6 and 14 respectively) in ^-MSH which prevents the 

 common sequence from extending to eleven amino acids. 



All three molecules possess melanocyte-stimulating activity, but, whereas 

 a-MSH and ^-MSH appear to have approximately comparable potencies, 

 corticotropin is of the order of a hundred times less active (Lee and Lerner, 

 1956) than a-MSH when assayed according to the method of Shizume, 

 Lerner and Fitzpatrick (1954). 



Shepherd et al. (1956) showed that active degradation products of 

 /3-corticotropin (e.g. the A^-terminal fragment containing 24 amino acid 

 residues) retained the same ratio of melanocyte-stimulating to adreno- 

 corticotropic activity as undegraded j3-corticotropin (39 amino acid residues), 

 and this important observation was in itself a strong indication that the 

 essential requirements for melanocyte-stimulating activity were to be found 

 within the smallest active corticotropin molecule. The amino acid sequence 



* The presence of A^-acetylserine as the A^-terminal group in a-MSH has now been 

 confirmed. When peptide CHi (Fig. 2) was subjected to hydrazinolysis both acetylhydrazide 

 and serine hydrazide were formed and were identified as described by Fraenkel-Conrat and 

 Narita (p. 260).— Ed. 



