N(7)-PROTONATION-INDUCED CONFORMATIONAL FLIPPING IN HYPERMODIFIED NUCLEIC-ACID BASE N-6-(N-GLYCYLCARBONYL) ADENINE

Protonation-induced conformational changes are studied in the hypermod ified nucleic acid base N-6-(N-glycylcarbonyl) adenine, gc(6)Ade, usin g the quantum chemical perturbative configuration interaction using lo calised orbitals method. Protonation at the N(7) position of adenine i n gc(6)Ade induces reorientation of the N-6 substituent, so as to allo w stabilisation through an intramolecular hydrogen bond involving N(7) H and the carbonyl oxygen in the glycylcarbonyl substituent. The relat ive orientation of the carboxyl group with respect to the carbonyl gro up in the ureido HN-CO-NH linkage is predicted to be similar to that i n unprotonated gc(6)Ade. The theoretically preferred proximal conforma tion of N(7)-protonated gc(6)Ade restores the participation of N(6)H a nd 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.