Synthesis of Nucleosides and Nucleotides 165 



extent to which adenine is incorporated under similar con- 

 ditions. This trace utihzation of guanine now makes the 

 difference between the rat and the mouse a large quantitative 

 one rather than the heretofore apparent qualitative one. 

 These species differences also indicate that caution must be 

 exercised in drawing generalizations in this field. 



In the survey of the utilization of various purines by the rat 

 the individual purines were isolated from the tissue nucleic 

 acids. However, upon the recognition by Carter and Cohn 

 (1949) that two isomeric adenylic acids and two guanylic 

 acids could be obtained upon alkaline hydrolysis of pentose 

 nucleic acids, it became of interest to know whether these 

 isomers could be differentiated on any metabolic basis. 

 The incorporation of [1,3-^^N2;8-^*C] adenine into the indi- 

 vidual nucleotides (Marrian, Spicer, Balis and Brown, 1951) 

 was studied and the results did not indicate any preferential 

 incorporation into either of the isomers of adenylic acid or of 

 guanylic acid. In those experiments it was also demonstrated 

 that there was a parallel incorporation of the two labelling 

 isotopes into each of the purines, and this further sub- 

 stantiated an earlier conclusion that the purine ring is 

 retained intact during the process of transformation of adenine 

 into polynucleotide guanine. 



Approaches to the Biosynthesis and Synthesis of 

 Nucleosides and Nucleotides 



Our programme is aimed at the elucidation of the immedi- 

 ate precursors of nucleic acids in the hope of providing a 

 rational approach to the design of antimetabolites of possible 

 chemotherapeutic import. We have therefore wished to 

 investigate the utilization of labelled nucleosides and nucleo- 

 tides, compounds which are intermediate in size between the 

 bases and the polynucleotides. 



The first approach to these compounds involved the growth 

 of yeast in a medium containing isotopic ammonia. The 

 yeast (pentose) nucleic acid was then isolated and four 

 nucleotides have now been isolated by chemical procedures 



