Incorporation of 2,6-diaminopurine into the nucleoside phosphates of the mouse.

It has been shown (a) that the inhibition of Lactobacillus casei by high concentrations of 2,6-diaminopurine (2,6-DAP) in a folic acid-containing medium is reversible only by adenine, while in a thymine-containing medium adenine is more effective than other purines in restoring growth (l), (b) that 2,6-DAP is extensively utilized as a precursor of both polynucleotide adenine and polynucleotide guanine by L. casei (2), (c) that an L. casei mutant can utilize 2,6-DAP riboside as the sole purine source while the wild strain cannot (3, 4), and (d) that 2,6-DAP is incorporated into the pentose nucleic acid (PNA) guanine of the rat (5). On the basis of these findings it was suggested that the inhibitory activity of 2,6-DAP is probably due to competition with adenine for incorporation into some specific adenine-containing product, such as adenosinetriphosphate (ATP) or certain coenzymes, rather than to an interference with PNA synthesis or purine interconversion. The fact that Kornberg and Pricer demonstrated (6) that 2,6-DAP riboside can be enzymatically phosphorylated and can be converted to 2-aminoadenosinetriphosphate lends support to this suggestion. As part of a program to investigate the mechanisms of action of certain known anti-cancer agents, the trichloroacetic acid-extractable nucleoside phosphates of mice which had received injections of radioactive 2,6-DAP were examined in an effort to see whether this purine as such can be incorporated into nucleotides.