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Abstract Hydrophobic interactions are one of the fundamental driving forces of self‐assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson–Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single‐stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interaction. We demonstrate a versatile hydrophobicity‐guided higher‐order assembly strategy by employing strategically engineered DNA nanostructures of increasing complexity, ranging from simple DNA tiles to complex origami structures, functionalized with these small hydrophobic molecules as programmable building blocks.
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Complex Donuts: Small Variations in DNA Sequence Dictate Pathway Complexity in DNA Nanotoroids
Abstract The formation of higher‐order structures in natural biopolymers, such as polypeptides and nucleic acids, is governed by sequence specificity and monomer chemistry. Although nucleic acids can assemble into programmable nanostructures through base‐pairing interactions, their chemical diversity is limited to four nucleobases. DNA amphiphiles overcome this limitation by introducing orthogonal interactions through non‐nucleosidic modifications. These amphiphiles self‐assemble into diverse morphologies, such as spheres, fibers, or sheets, with closely packed, parallel DNA strands on their exterior. This unusual arrangement can give rise to emergent properties absent in simple DNA strands. Here, we show that the precise sequence of single‐stranded DNA, independent of double helix base‐pairing, can be used to program the self‐assembled morphology of DNA amphiphiles. Remarkably, small sequence variations can drive the formation of nonequilibrium DNA nanotoroids, rather than conventional morphologies. The DNA nanotoroids were formed as on‐pathway structures via a competitive mechanism, only when a toroid‐selective DNA sequence was used. They could be stabilized noncovalently by a small molecule cross‐linker or coassembly with a secondary DNA amphiphile. Molecular dynamics simulations demonstrated the dependence of toroid formation on the structure of the end π‐stacking unit. This work introduces a new class of DNA‐based nanotoroid materials with assembly properties controlled by unique sequences, akin to proteins, for applications in cell delivery, nanofiltration, nanoreactors, and materials templation.
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- Award ID(s):
- 2410514
- PAR ID:
- 10667889
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Angewandte Chemie
- Volume:
- 137
- Issue:
- 33
- ISSN:
- 0044-8249
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/ange.202501441
