Structural grounds for the 2-aminopurine mutagenicity: a novel insight into the old problem of the replication errors

Abstract

Within the framework of the classical Watson–Crick tautomeric hypothesis it has been reliably established by quantum-chemical calculations that amino–imino tautomerization of the 2-aminopurine (2AP), implemented in any way present in the literature, is not the root cause of its mutagenicity. It has been shown for the first time that the mutagenic pressure of the 2AP is exerted on DNA by the generation of the T* mutagenic tautomers (marked by an asterisk) within the 2AP·T(WC) pair with Watson–Crick (WC) geometry at its transformation into the wobble (w) pair, 2AP·T*(w), according to the reaction pathway 2AP·T(WC) → 2AP·T*(w). This mutagenic process proceeds with considerably greater probability than in the case of the Watson–Crick A·T(WC) DNA base pair tautomerization – A·T(WC) → A·T*(w).