Comparative mutagenicities of N6-methoxy-2,6-diaminopurine and N6- methoxyaminopurine 2'-deoxyribonucleosides and their 5'-triphosphates

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Abstract
The structure of the deoxyribonucleoside derived from N6-methoxy-2,6-diaminopurine (dK) was examined by NMR. The methoxyamino residue was found predominantly in the imino rather than the amino tautomer (ratio: 9:1 in DMSO). The nucleoside proved to be a potent transition mutagen in Escherichia coli, in contrast to the closely related nucleoside derived from the analogue N6-methoxyaminopurine (dZ), which was only weakly mutagenic. The 5′-triphosphate derivatives, dKTP and dZTP, were synthesized; Taq polymerase incorporated dKTP opposite both T and, less well, opposite dC in template DNA. Both analogue triphosphates produced transition mutations when added to PCR reactions. In each case, there was a large excess of AT→GC compared to GC→AT mutations (ratios were 15:1 for dKTP and 10:1 for dZTP). Polymerase extension times in each cycle had to be extended, consistent with a decreased rate of DNA synthesis in the presence of the analogues. This and the mutagenic ratios are discussed in terms of syn-anti inversion of the methoxyl group.