494 R. E. HANDSCHUMACHER AND A. D. WELCH 



the metabolism of nucleic acids or nucleotide-containing coenzymes. 298 At- 

 tempts to reverse the inhibitory effects of this compound on the growth of 

 L. casei have indicated that it is a weak antagonist of folic acid, probably by 

 virtue of its diaminopyrimidine nucleus. 302 More specific and complete pre- 

 vention of the effects of diaminopurine have been noted with purines, par- 

 ticularly adenine, e.g., with L. casei, 302 E. coli, 313 Aerobacter aerogenes, 301 

 vaccinia virus growing in chick embryo tissue, 305 and sarcoma-180 cells in 

 culture. 312 



Metabolic studies with N 15 - or C 14 -labeled diaminopurine indicated clearly 

 that conversion of this purine derivative into nucleic acid guanine was a 

 prominent aspect of its metabolism. 291, 292 Minor incorporation in the form 

 of nucleic acid adenine was also noted, 295 ' 296 but no unchanged diamino- 

 purine was detected. A partially purified nucleoside phosphorylase from 

 beef liver formed guanosine from diaminopurine and ribose-1-phosphate 313 ; 

 presumably deamination occurred after condensation with ribose, since 

 diaminopurine ribonucleoside, 314 but not the free purine, is a substrate for 

 the deaminase contaminating this preparation. The 8-hydroxy derivative 

 of diaminopurine is formed during its incubation with xanthine oxidase 

 from milk. 315 Reaction of diaminopurine ribonucleoside w T ith a purified 

 phosphokinase from yeast (which is apparently specific for adenosine and 

 diaminopurine ribonucleoside) gave the monophosphate; in turn, this re- 

 acted with ATP to form the corresponding di- and triphosphates. 316 These 

 ribonucleotides also have been detected in the tissues of mice after the ad- 

 ministration of diaminopurine. 317 Following incubation of diaminopurine 

 with resting cell suspensions of E. coli, diaminopurine ribonucleotides and 

 2-methylaminoadenine ribonucleotides, as well as 2-methylamino-6-hy- 

 droxypurine and xanthine, have been isolated from the acid-soluble com- 

 ponents. 318 The latter compounds, but not the ribonucleotides, were formed 

 from diaminopurine by suspensions of a resistant strain of this organism. 



308 R. Hertz and W. W. Tullner, Science 109, 539 (1949). 



309 G. E. Cartwright, J. G. Palmer, G. H. Hitchings, G. B. Elion, F. D. Gunn, and 

 M. M. Wintrobe, J. Lab. Clin. Med. 35, 518 (1950). 



310 J. J. Biesele, R. E. Berger, A. Y. Wilson, G. H. Hitchings, and G. B. Elion, Cancer 

 4, 186 (1951). 



3,1 J. H. Burchenal, D. A. Karnofsky, E. M. Kingsley-Pillers, C. M. Southam, W. P. 

 L. Myers, G. C. Escher, L. F. Craver, H. W. Dargeon, and C. P. Rhoads, Cancer 4, 

 549 (1951). 



312 J. J. Biesele, R. E. Berger, and M. Clarke, Cancer Research 12, 465 (1952;. 



313 E. D. Korn and J. M. Buchanan, J. Biol. Chem. 217, 183 (1955). 



314 J. Davoll and B. A. Lowy, J. Am. Chem. Soc. 73, 1650 (1951)-. 



315 J. B. Wyngaarden, J. Biol. Chem. 224, 453 (1957). 



316 A. Romberg and W. E. Pricer, Jr., J. Biol. Chem. 193, 481 (1951). 



317 G. P. Wheeler and H. E. Skipper, J. Biol. Chem. 205, 749 (1953). 



318 C. N. Remy and M. S. Smith, J. Biol. Chem. 228, 325 (1957). 



