Tuning the Cavity Size and Chirality of Self-Assembling 3D DNA Crystals

Journal of the American Chemical Society

4 years ago

Tuning the Cavity Size and Chirality of Self-Assembling 3D DNA Crystals

Yan Liu, Chad R. Simmons, Nadrian C. Seeman, Tara MacCulloch, Hao Yan, Fei Zhang, Nicholas Stephanopoulos, Noureddine Fahmi

The foundational goal of structural DNA nanotechnology—the field that uses oligonucleotides as a molecular building block for the programmable self-assembly of nanostructured systems—was to use DNA to construct three-dimensional (3D) lattices for solving macromolecular structures. The programmable nature of DNA makes it an ideal system for rationally constructing self-assembled crystals and immobilizing guest molecules in a repeating 3D array through their specific stereospatial interactions with the scaffold. In this work, we have extended a previously described motif (4 × 5) by expanding the structure to a system that links four double-helical layers; we use a central weaving oligonucleotide containing a sequence of four six-base repeats (4 × 6), forming a matrix of layers that are organized and dictated by a series of Holliday junctions. In addition, we have assembled mirror image crystals (l-DNA) with the identical sequence that are completely resistant to nucleases. Bromine and selenium derivatives were obtained for the l- and d-DNA forms, respectively, allowing phase determination for both forms and solution of the resulting structures to 3.0 and 3.05 Å resolution. Both right- and left-handed forms crystallized in the trigonal space groups with mirror image 3-fold helical screw axes P3₂ and P3₁ for each motif, respectively. The structures reveal a highly organized array of discrete and well-defined cavities that are suitable for hosting guest molecules and allow us to dictate a priori the assembly of guest–DNA conjugates with a specified crystalline hand.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b06485

DOI: 10.1021/jacs.7b06485