Pseudo Base Pairs that Exhibit High Duplex Stability and Orthogonality through Covalent and Non-covalent Interactions

Natural base pairs stabilize nucleic acid duplexes via hydrogen bonding and stacking interactions, and efforts have been made to identify artificial base pairs that stabilize duplexes through different interactions. Herein, we describe our attempts to prepare pseudo base pairs that exhibit high stability and orthogonality. Pairs of azobenzene derivatives showed unexpectedly high stability and orthogonality due to intermolecular stacking interactions. Pairs of cationic molecules showed even higher stability than natural G-C pairs through both electrostatic and stacking interactions. Duplexes can be crosslinked via [2+2] photocycloaddition between stilbene derivatives, and pairs of non-planar cyclohexane derivatives can stabilize duplexes by hydrophobic interactions rather than stacking interactions. Hetero-selective pairing can be achieved using electron donor acceptor interactions. These pseudo base pairs would work well as building blocks in nanotechnology and biotechnology due to their unique functionalities.

Automated summary

In this study, artificial base pairs with high stability and orthogonality were identified, such as azobenzene and cationic molecule pairs. These pairs showed higher stability than natural G-C pairs through stacking and electrostatic interactions. Additionally, crosslinking and stabilization of duplexes were achieved through photocycloaddition and hydrophobic interactions.