Metabolism of 2, 6-diaminopurine; conversion to 5'-phosphoribosyl-2-methylamino-beta-aminopurine by enzymes of Escherichia coli.

Since Hitchings et al. (1, 2) first demonstrated that 2,6-diaminopurine inhibited Lactobacillus casei, DAPl has been shown to inhibit growth or multiplication in a wide variety of biological systems including mammals, tumors, birds, plants, viruses, and numerous bacteria. Although DAP is not incorporated per se into the nucleic acids, incorporation does occur after conversion to adenine and guanine (3-6). The metabolic fate of DAP generally parallels that of guanine. Thus, DAP has a dual metabolic fate, as it may serve either as an inhibitor or, when its inhibitory action is blocked, as a precursor for nucleic acid purines (5). DAP may exert its inhibitory properties by being converted into inhibitory analogues of adenine-containing cofactors such as ATP, DPN, and FAD (5). The competition between adenine and DAP may occur either in the formation of the nucleotides or in their function. Wheeler and Skipper have shown that DAP is incorporated into the ATP fraction of mouse tissue (7). Kornberg and Pricer demonstrated that DAP riboside may be enzymatically phosphorylated to a DAP analogue of ATP (8). To observe the phenomenon of DAP resistance in Escherichia coli, strain B, a study was conducted to determine whether growth inhibition by DAP could be correlated with the formation of DAP nucleotides. Although DAP nucleotides were isolated from the acid-soluble fraction, the isolation and identification of MeDAP and the corresponding 5’phosphoribosyl derivative revealed that methylation of DAP at the 2amino position was a new and quantitatively significant pathway of DAP metabolism in E. coli.