#'f '^"^"ê'^^i:"-^ ^> V^r''-^""^^^^"^ 



The structure and activity of melanocyte- 

 stimulating and adrenocorticotropic peptides 



J. lEUAN HARRIS* 



Department of Biochemistry, University of Cambridge 



The isolation of highly purified melanocyte stimulating substances from pig 

 posterior pituitary extracts has been reported from several different labora- 

 tories during the past two years. (Lerner and Lee, 1955; Lee and Lerner, 

 1956; Porath, Roos, Landgrebe and Mitchell, 1955; Benfey and Purvis, 

 1955; Geschwind, Li and Bamafi, 1956.) 



The material isolated by Lerner and Lee (1955) was found to be a highly 

 basic polypeptide with an isoelectric point of 11 -0-1 1-5, whilst both Porath 

 et al. (1955) and Geschwind et al. (1956) reported isoelectric points of 5-2 

 and 5-8, respectively, for the melanocyte stimulating hormone (MSH) pre- 

 parations which they had isolated. This apparent discrepancy was later re- 

 solved when Lee and Lerner (1956) showed that both forms of the hormone 

 were present in the same extracts of pig posterior pituitaries. Consequently 

 they proposed that the basic polypeptide which they had originally isolated 

 be called a-melanocyte-stimulating hormone (a-MSH), and that the acidic 

 polypeptide hormone isolated in the other laboratories be called ^-melanocyte 

 stimulating hormone (j3-MSH). 



THE iS-MELANGCYTE-STIMULATING HORMONE 



(iS-MSH) 



The complete structure of j8-MSH was elucidated by Harris and Roos 

 (1956) using material prepared by Roos according to the isolation procedure 

 of Porath et al. (1955). The amino acid sequence of the peptide hormone 

 was deduced from the results of 'stepwise' degradation studies on the intact 

 molecule and from the characterization of peptide fragments isolated after 

 digestion with trypsin and chymotrypsin, as shown in Fig. 1. In this way 

 iS-MSH was shown to consist of eighteen amino acid residues in a single 

 polypeptide chain, and to contain a sequence of seven amino acids, 

 Met.Glu.His.Phe.Arg.Try.Gly. (positions 7-13), which had previously been 

 shown to occur in the corticotropins (e.g. Bell, 1954); in addition, the tyro- 

 sine and proline residues, in positions 5 and 15, respectively, also occur in 



* Member of the Scientific Staff of the Medical Research Council. 



