N(7)-protonation-induced conformational flipping in hypermodified nucleic acid base N6-(N-glycylcarbonyl) adenine

Protonation-induced conformational changes are studied in the hypermodified nucleic acid base N6-(N-glycylcarbonyl) adenine, gc6Ade, using the quantum chemical perturbative configuration interaction using localised orbitals method. Protonation at the N(7) position of adenine in gc6Ade induces reorientation of the N6 substituent, so as to allow stabilisation through an intramolecular hydrogen bond involving N(7)H and the carbonyl oxygen in the glycylcarbonyl substituent. The relative orientation of the carboxyl group with respect to the carbonyl group in the ureido HNCONH linkage is predicted to be similar to that in unprotonated gc6Ade. The theoretically preferred proximal conformation of N(7)-protonated gc6Ade restores the participation of N(6)H and N(1) in the Watson-Crick base pairing similar to that in unmodified adenine. This unique orientation can be significant for altering the reading frame in codon-anticodon interactions.