V. si'KciFK rr^' or action 155 



aspnrt ic .-icid iiiliil)its ni'ou t li and licnutiilohiii tonnatioii in tlic diick, tlic 

 iiiliihitioii I'atio hrinji; ai)i)i'<)\iinalt'ly .")()(), l»ut has no clTcct. on I'jils at a 

 level of 1.') lu^. per day. 



Kirsanova and 'rrufanov"'- found tluitthe corresponding (i-earhon analog, 

 pteroylaminoadipic acid, was 5% as active as PGA for the chick and 10 to 

 20 % as active as PGA for the rat. Similarly, the 7-carbon analog, pteroyl- 

 aininopimelic acid," was about 10% as active as PGA for L. cami, 20% as 

 active for rats, and 50% as active for chicks. 



Wright ct alJ^ found that the pteroyl derivatives of alanine, t-amino- 

 caproic, cystine, phenylalanine, serine, and valine were neither stimulatory 

 nor inhibitory activity. The jS-alanine, methionine, and sarcasine derivatives 

 had slight growth-promoting activity for S. faecalis R. 



6. Alkyl Deriv.\tives 



Alkyl derivatives of PGA have been prepared in which the methyl group 

 has been added to the pteridine ring,''^' ^^ to the C^ position" and the N^" 

 position, ^^ and to the 2-amino group.''^ 



a. Biological Experiments with "x Methyl PGA" 



Martin et al?^ first described a PGA antagonist designated 7-methyl- 

 pteroyl-D-glutamic acid which had an inhibition index of 150 for*S. faecalis 

 \i. This was prepared by the condensation of 2 , 4 , 5-triamino-(3-hydroxy- 

 pyrimidine with a,^-dibromobutyraldehyde and p-aminobenzoyl-D-glu- 

 tamic acid. The methyl group was ascribed to the 7 position of the pteridine 

 ring, although this fact has not yet been definitely established. 



The biological properties of a similar compound have been described by 

 Franklin et alJ'" in which the natural l isomer of jj-aminobenzoylglutamic 

 acid was used. The inhibition index of the crude reaction product desig- 

 nated crude ''x methyl PGA" is 30 for S. faecalis, 1000 for L. casei, and 3000 

 for rats. The inhibition indices for microorgani.sms are relatively constant 

 over large ranges of concentration, and the inhil)ition produced in rats is 

 completely reversible l)y PGA. The syndrome produced in rats by the 

 antagonist is similar to, but more acute, than that induced by feeding a pu- 

 rified diet plus sulfasuxidine and was accompanied l)y oral lesions. Reversal 



^- v. A. Kirsanova and A. V. Trufanov, Biokhimi/a 15, 243 (1950). 

 " V. A. Kirsanova and A. V. Trufanov, Biokhimya 16, 367 (1951). 

 '^ W. B. Wright, Jr., D. B. Cosulich, M. J. Fahrenbach, C. W. Waller, J. M. Smith, 



.Jr., and M. E. Hultquist, J. Am. Chem. Soc. 71, 3014 (1949). 

 ■ A. L. Franklin, E. L. R. Stokstad, M. Belt, and T. H. Jukes, 169, 427 (1947). 



G. J. Martin, L. Tolman, and J. Moss, Arch. Biochem. 12, 318 (1947). 

 " M. E. Hultquist, J. M. Smith, Jr., D. R. Seeger, D. B. Cosulich, and E. Kuh, 



J . Am. Chem. Soc. 71, 619 (1949). 

 "s B. Roth, J. M. Smith, Jr., and M. E. Hultquist, J. Am. Chem. Soc. 73, 2864 (1951). 



