METABOLITE ANTAGONISTS 



237 



acid antagonist may be overcome, at least in part, by the action of second- 

 ary metabolites as well as the primary metabolite. The toxic effect of 

 3-acetylpyridine on rats is reversed by either nicotinic acid amide or 

 tryptophane (Woolley, 1945a). 



Analogues. Mitchell and Niemann (1947) found that the halogenated 

 derivatives of phenylalanine and tyrosine competitively inhibit growth 

 of the wild strain of Neurospora crassa (Table 42). The most effective 

 of these inhibitors was 3-fiuoro-DL-phenylalanine. The structural form- 

 ulas for this analogue and the natural metabolite are shown below: 



^^-CHo— CHNH2— COOH 



/\ 



CHo— CHNH2— COOH 



V 



Phenylalanine 



3-Fluorophenylalanine 



Table 42. Inhibition of Growth of Neurospora crassa by Some Halogenated 



Alpha-amino Acids 

 Basal medium contained 30 mg. of DL-phenylalanine or 20 mg. L-tyrosine per liter 

 depending upon the antagonist tested. (Mitchell and Niemann, Jour. Am. Chem. 

 Sac. 69, 1947. Published by permission of the American Chemical Society.) 



The other halogen derivitives (chloro, bromo, and iodo) were less effective 

 inhibitors. 3-Fluorophenylalanine was shown to be an effective inhibitor 

 for various other fungi and bacteria. 



The effect of j8-2-thienylalanine on the growth of a strain Saccharomyces 

 cerevisiae and certain bacteria has been studied by Ferger and Du 

 Vigneaud (1948). The formula for this thiophene analogue of phenyl- 

 alanine is given below: 



HC C— CHo— CHNH2— COOH 



HC 



CH 



i3-2-Thienylalanine 



Only the l isomer is active in competing with phenylalanine. The replace- 

 ment of divalent sulfur ( — S — ) by a vinylene group ( — CH=CH — ), or 

 vice versa, often leads to the production of an antimetabolite. As 

 another example, the effect of replacing sulfur in cysteine by radicals 



