Molecular orbital elucidations on mechanisms for repair of alkylated nucleosides

Abstract

Experimental findings have indicated that purine nucleosides alkylated at the N⁷-guanine site are repaired by removal of the entire base moiety through spontaneous depurination or glycosylasemediated base-excision. Repair of nucleosides alkylated at the O⁶-guanine and O⁴-thymine positions, however, is mediated by an alkyltransferase which removes only the alkyl group. The chemical reasons behind these specific choices of repair mechanisms are brought to light through semiempirical molecular orbital calculations, which provide a correct assignment of mechanism to each class of alkylated nucleosides in good accord with experiment.