V. SPKCIFICITY OF ACTION 149 



x;iiitlu)i)((,M'iii (lid not lead to the appearance of any labeled cai'hoii in liu; 

 PGA isolated from the hoinogeuate. 



B. PGA ANTAGONISTS 



The study of PGA antagonists has proved to have both academic and 

 clinical interest. These compounds have facihtated the study of the mech- 



TABLK V 

 Types of PGA Antagonists 



1. Pvrimiiliue derivatives 



Example: o-Xitrouracil (Hitchiugs et al.^^) 



2. Purine derivatives 



Example: 2,4-Diamiiiopuriiie (Elion*^) 



3. Pteridiue derivatives 



Example: 2,4-Diamino-6,7-diphenylpteridine (Daniel et al.^^) 



4. Modification of pterin nucleus 



Example: Quinoxaline-2-carhoxyl-p-aminol)onzoylglutamic acid (Woolley and 

 Pringle*'') 



5. Pteroyl derivatives of different amino acids 

 'Example: Pteroylaspartic acid (Hutchings et al.^'') 



6. Alk\-1 derivatives of pterojlglutamic acid 



Example: N"-Methylptero3'lglutamic acid (Cosulich and Smith^*) 



7. Substitution on the pterin nucleus 



Example: 4-Aminopteroylglutamic acid (Seeger et. al.^^) 



8. Sulfur analogs with a sulfonyl group in place of the carboxj-l of p-aminobenzoic 

 acid 



Example: Iienzimidazole-2-methyl-p-aminobonzene sulfonylglutamic acid (Ed- 

 wards et. al.^") 



anism of PGA function in microorganisms and in tissues of higher animals. 

 They have also provided new tools for the study of leukemic processes and 

 have proved to have some clinical application in the therapy of leukemia. 

 A complete cataloguing of the antagonists which have been synthesized 

 is well outside the scope of this review. For more detailed information the 

 reader is referred to the excellent reviews by Shive" and Martin. ^^ The 



" G. J. Martin, Biological Antagonism. Blakiston & Co., New York, 1952. 



"G. B. Hitchings, G. B. Elion, E. A. Falco, P. B. Russell, and H. Vander Wcrff, 



Ann. X. Y. Acad. Sci. 52, 1318 (1950). 

 *' G. B. Elion and G. B. Hitchings, ./. Binl. Chcm. 187, 511 (1950). 



