Design of Orthogonal DNA Sticky-End Cohesion Based on Configuration-Specific Molecular Recognition

In sticky-end cohesion, sequence complementarity is the key to design specific recognition among many DNA nanostructure units. The binding orthogonality usually arises from sticky-end pairs of different sequences. Instead of creating orthogonal species of sticky-end bonds based on sequence complementarity, we restricted the sticky-end sequence diversity down to the fixed C–G pair and explored orthogonal recognition of the synthetic DNA constructs based solely on the configurational match. From our comprehensive investigations of 2D tessellation and 3D crystallization, we demonstrated the new configuration-specific sticky-end cohesion to program specific and precise molecular recognition of synthetic structural units for high-order DNA self-assembly.