Complementary Nucleobase Interaction Enhances Peptide–Peptide Recognition and Self‐Replicating Catalysis

The availability of the complementary interaction of nucleobases for influencing the formation of peptide architectures was explored. Nucleobases were incorporated as additional recognition elements in coiled‐coil peptides by employing nucleobase amino acids (NBAs), which are artificial L ‐ α ‐amino γ ‐nucleobase‐butyric acids. The effect of the base‐pair interaction on intermolecular recognition between peptides was evaluated through a self‐replication reaction. The self‐replication reactions of the peptides with complementary base pairs such as thymine–adenine or guanine–cytosine at the g–g ′ heptad positions were accelerated in comparison with those of the peptides with mismatched base pairs or without nucleobases. However, thymine–adenine pairs at the e–e ′ positions did not enhance the self‐replication. In the presence of a denaturant, the enhancement effects of complementary base pairs on the reaction disappeared. Thermal denaturation studies showed that the thymine–adenine pairs contributed to stabilization of the coiled‐coil structure and that the pairs at the g–g ′ positions were more effective than those at the e–e ′ positions. The peptide–peptide interaction was reinforced by complementary nucleobase interactions appropriately arranged in the peptide structure; these led to acceleration of the self‐replication reactions.