276 BACTERIOPHAGES 



principle to demonstrate that synthesis of phage-precursor DNA 

 is independent of synthesis of phage-precursor protein. 



d. Prevention of DNA Synthesis 



Specific attack against the nucleic acid metabolism of phage- 

 infected bacteria has been attempted with a number of structural 

 analogues of the purine and pyrimidine bases. Inhibitions have 

 been reported in experiments with bacteria and phage, but the 

 effects on DNA synthesis were usually not tested. The anti- 

 purines whose eff'ects on phage production are significant enough 

 to warrant further analyses include those with triazine or triazole 

 substitutions (Matthews and Smith, 1955; Wooley, Murphy, 

 Bond, and Perrine, 1952) and 2,6-diaminopurine (Asheshov, 

 Hall, and Flon, 1955). The latter deserves special attention 

 since it is able to eliminate kappa from paramecia (Stock, 

 Jacobson, and Williamson, 1951). 



The antipyrimidines of particular interest are those which act 

 as thymine antagonists by virtue of a halogen substitution in the 

 5 position. These do not prevent DNA synthesis but may be 

 incorporated into the DNA molecule in place of thymine. The 

 effects of this incorporation on phage activity will be considered 

 in a later section of this chapter. The presence of the unique 

 pyrimidine, 5-(hydroxymethyl)cytosine, in the DNA of T2 and 

 related phages should off'er a possible target for specific attack. 

 Under special conditions where this pyrimidine can act as a 

 growth factor for bacterial auxotrophs which require the 

 pyrimidine moiety (2-methyl-5-(hydroxymethyl)cytosine) of 

 thiamine for growth, "methioprim" (the 2-methylmercapto 

 derivative) behaves as a competitive inhibitor of 5-(hydroxy- 

 methyl)cytosine. The production of T2, however, is not 

 aff'ected by this analogue (Gots, unpublished observations). 



e. Prevention of Coenzyme Activity 



Structural analogues of the B vitamins are known to act as 

 specific competitive inhibitors of either the synthesis or function 



