586 NEW AND UNIDENTIFIED GROWTH FACTORS 



Support for the concept of an intrinsic growth-promoting property as- 

 sociated with the serine-glycine-glutamic acid structure is provided by the 

 experiments of Chattaway and coworkers.'^' ^'^ They found that extracts of 

 liver and yeast contained growth-promoting agents for C. diphiheriae 

 gravis, S. faecalis R., and L. casei, which upon concentration proved to be 

 of peptide nature. Two peptides, labeled Pi and P2 , contained the bulk of 

 the activity; P2 upon hydrolysis was found to yield serine, glycine, and 

 glutamic acid. Finally, the experiments of Krehl and Fruton'^^ have con- 

 firmed the activity of L-serylglycyl-L-giutamic acid for L. casei and have 

 shown that the closely related L-seryl-L-alanyl-L-glutamic acid was in- 

 active.'^^'^ Also inactive were several related peptides of glutamic acid, 

 glycine, and tyrosine. 



Peptides of other amino acids have also been shown to be more active 

 than their constituent moieties in supporting microbial growth. Malin et 

 alJ^ reported that certain peptides of glycine were utilized more readily 

 by several lactobacilli than was glycine itself. Simmonds and Fruton ob- 

 served" ' ^° that a prolineless mutant of E. coli Avas more responsive to any 

 of several proline peptides tested than it was to proline, and that an isolated 

 species of Alcaligenes, termed "SF",^i required leucyl peptides for growth; 

 with these in the medium, no other nitrogen or carbon source was needed. 

 Other peptide requirements have been demonstrated by Snell et al.f^'^^ in 

 a medium in which D-alanine satisfied the vitamin Be requirement, L. casei 

 could be shown also to depend upon a peptide factor for its nutrition. Frac- 

 tionation of the factor from partly hydrolyzed casein produced a mixture 



" F. W. Chattaway, F. C. Happold, and M. Sandford, Biochem. J. 38, 111 (1944). 



" F. W. Chattaway, D. E. Dolby, D. A. Hall, and F. C. Happold, Biochem. J. 45, 

 592 (1949). 



'^ W. A. Krehl and J. S. Fruton, J. Biol. Chem. 173, 479 (1948). 



'^* Although recent reports on the structure of insulin'^- '''' fail to reveal a serine- 

 glycine-glutamic acid sequence, the closest relatives are a cysteine-glycine-glu- 

 tamic acid, and a cysteine-glycine-serine series. Both of these are found in the 

 "phenylalanine" fraction of insulin rather than in the "glycine" fraction where 

 strepogenin activity was first reported.''" However, the similarity of the first se- 

 quence listed here to the strepogenin-active compound (serine replaced by cys- 

 teine) may warrant the testing of additional peptides. 



76 F. Sanger and H. Tuppy, Biochem. J. 49, 481 (1951). 



" F. Sanger and E. O. P. Thompson, Biochem. J. 53, 366 (1953). 



78 R. B. Malin, M. N. Camien, and M. S. Dunn, Arch. Biochem. and Biophys. 32, 106 

 (1951). 



73 S. Simmonds and J. S. Fruton, /. Biol. Chem. 174, 705 (1948). 



8" S. vSimmonds and J. S. Fruton, /. Biol. Chem. 180, 635 (1949). 



s' S. Simmonds and J. S. Fruton, Science 109, 561 (1949). 



S2 H. Kihara, W. G. McCullough, and E. E. Snell, ./. Biol. Chem. 197, 783 (1952). 



«3 H. Kihara and E. E. Snell, ./. Biol. Chem. 197, 791 (1952). 



8" H. Kihara, (). A. Klatt, and E. E. Snell, ./. Biol. Chem. 197, 801 (1952). 



