Tailored protein encapsulation into a DNA host using geometrically organized supramolecular interactions
Andreas Sprengel and Barbara Sacca
: J Nanomater Mol Nanotechnol
The self-organizational properties of DNA have been used to realize synthetic hosts for protein encapsulation. However, current strategies of DNAâprotein conjugation still limit true emulation of natural hostâguest systems, whose formation relies on noncovalent bonds between geometrically matching interfaces. Here, we report one of the largest DNAâprotein complexes of semisynthetic origin held in place exclusively by spatially defined supramolecular interactions. Our approach is based on the decoration of the inner surface of a DNA origami hollow structure with multiple ligands converging to their corresponding binding sites on the protein surface with programmable symmetry and range-of-action. Our results demonstrate specific hostâguest recognition in a 1:1 stoichiometry and selectivity for the guest whose size guarantees sufficient molecular diffusion preserving short intermolecular distances. DNA nanocontainers can be thus rationally designed to trap single guest molecules in their native form, mimicking natural strategies of molecular recognition and anticipating a new method of protein caging.