On the role of 2,6-diaminopurine in the biosynthesis of nucleic acid guanine.

It has been demonstrated (1, 2) that dietary guanine is not utilized to a significant extent by the rat for nucleic acid synthesis but that adenine may be utilized by the rat as a precursor of both polynucleotide adenine and polynucleotide guanine (2). Recent studies with labeled glycine (3) and nucleic acid (4) have indicated that polynucleotide guanine may also arise by mechanisms not involving the mediation of adenine. The mechanism by which adenine is converted into polynucleotide guanine remains an open question and the present communication deals with a consideration of certain possible routes by which this transformation might occur. These are outlined in the scheme in Fig. 1. The failure of isoguanine (III) (5) and of hypoxanthine (V) and xanthine (VI) (6) to serve as precursors of nucleic acid purines has already been noted. However, as was reported in a preliminary communication (7), 2,6-diaminopurine (IV) was found to be an effective precursor of nucleic acid guanine (II).’ The initial experiment was carried out with 2,6-diaminopurine labeled with heavy nitrogen, For the synthesis with N16, isotopic ammonium nitrate was fused with dicyandiamide to yield guanidine nitrate (8), which was condensed with malononitrile to give 2,4,5,6-tetraaminopyrimidine after nitrosation and reduction (9). 2,6-Diaminopurine, containing excess N16 in the 1 and 3 positions as well as in the a-amino group, was obtained by use of the formic acid-formamide method (10). The synthesis is outlined in Fig. 2.