An official website of the United States government
Abstract Peptide nucleic acids (PNAs) have primarily been used to achieve therapeutic gene modulation through antisense strategies since their design in the 1990s. However, the application of PNAs as a functional nanomaterial has been more recent. We recently reported thatγ‐modified peptide nucleic acids (γPNAs) could be used to enable formation of complex, self‐assembling nanofibers in select polar aprotic organic solvent mixtures. Here we demonstrate that distinctγPNA strands, each with a high density ofγ‐modifications can form complex nanostructures at constant temperatures within 30 minutes. Additionally, we demonstrate DNA‐assisted isothermal growth ofγPNA nanofibers, thereby overcoming a key hurdle for future scale‐up of applications related to nanofiber growth and micropatterning.
more »
« less
Modular self-assembly of gamma-modified peptide nucleic acids in organic solvent mixtures
Abstract Nucleic acid-based materials enable sub-nanometer precision in self-assembly for fields including biophysics, diagnostics, therapeutics, photonics, and nanofabrication. However, structural DNA nanotechnology has been limited to substantially hydrated media. Transfer to organic solvents commonly used in polymer and peptide synthesis results in the alteration of DNA helical structure or reduced thermal stabilities. Here we demonstrate that gamma-modified peptide nucleic acids (γPNA) can be used to enable formation of complex, self-assembling nanostructures in select polar aprotic organic solvent mixtures. However, unlike the diameter-monodisperse populations of nanofibers formed using analogous DNA approaches,γPNA structures appear to form bundles of nanofibers. A tight distribution of the nanofiber diameters could, however, be achieved in the presence of the surfactant SDS during self-assembly. We further demonstrate nanostructure morphology can be tuned by means of solvent solution and by strand substitution with DNA and unmodified PNA. This work thereby introduces a science ofγPNA nanotechnology.
more »
« less
- PAR ID:
- 10160881
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 11
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
ABSTRACT Dynamic and flexible nucleic acid models can provide current and future scientists with physical intuition for the structure of DNA and the ways that DNA and its synthetic mimics can be used to build self-assembling structures and advanced nanomachines. As more research labs and classrooms dive into the field of structural nucleic acid nanotechnology, students and researchers need access to interactive, dynamic, handheld models. Here, we present a 3D-printable kit for the construction of DNA and peptide nucleic acid (PNA). We have engineered a previous modular DNA kit to reduce costs while improving ease of assembly, flexibility, and robustness. We have also expanded the scope of available snap-together models by creating the first 3D-printable models of γPNA, an emerging material for nuclease- and protease-resistance nanotechnology. Building on previous research, representative nucleic acid duplexes were split into logical monomer segments, and atomic coordinates were used to create solid models for 3D printing. We used a human factors approach to customize 3 types of articulated snap-together connectors that allow for physically relevant motion characteristic of each interface in the model. Modules are easy to connect and separate manually but stay together when the model is manipulated. To greatly reduce cost, we bundled these segments for printing, and we created a miniaturized version that uses less than half the printing material to build. Our novel 3D-printed articulated snap-together models capture the flexibility and robustness of DNA and γPNA nanostructures. Resulting handheld helical models replicate the geometries in published structures and can now flex to form crossovers and allow biologically relevant zipping and unzipping to allow complex demonstrations of nanomachines undergoing strand displacement reactions. Finally, the same tools used to create these models can be readily applied to other types of backbones and nucleobases for endless research and education possibilities.more » « less
-
Abstract The combination of multiple orthogonal interactions enables hierarchical complexity in self‐assembled nanoscale materials. Here, efficient supramolecular polymerization of DNA origami nanostructures is demonstrated using a multivalent display of small molecule host–guest interactions. Modification of DNA strands with cucurbit[7]uril (CB[7]) and its adamantane guest, yielding a supramolecular complex with an affinity of order 1010m−1, directs hierarchical assembly of origami monomers into 1D nanofibers. This affinity regime enables efficient polymerization; a lower‐affinity β‐cyclodextrin–adamantane complex does not promote extended structures at a similar valency. Finally, the utility of the high‐affinity CB[7]–adamantane interactions is exploited to enable responsive enzymatic actuation of origami nanofibers assembled using peptide linkers. This work demonstrates the power of high‐affinity CB[7]–guest recognition as an orthogonal axis to drive self‐assembly in DNA nanotechnology.more » « less
-
null (Ed.)The flow of charge through molecules is central to the function of supramolecular machines, and charge transport in nucleic acids is implicated in molecular signaling and DNA repair. We examine the transport of electrons through nucleic acids to understand the interplay of resonant and nonresonant charge carrier transport mechanisms. This study reports STM break junction measurements of peptide nucleic acids (PNAs) with a Gblock structure and contrasts the findings with previous results for DNA duplexes. The conductance of G-block PNA duplexes is much higher than that of the corresponding DNA duplexes of the same sequence; however, they do not display the strong even−odd dependence conductance oscillations found in G-block DNA. Theoretical analysis finds that the conductance oscillation magnitude in PNA is suppressed because of the increased level of electronic coupling interaction between G-blocks in PNA and the stronger PNA−electrode interaction compared to that in DNA duplexes. The strong interactions in the G-block PNA duplexes produce molecular conductances as high as 3% G0, where G0 is the quantum of conductance, for 5 nm duplexes.more » « less
-
Abstract Structural DNA nanotechnology enables the self‐organization of matter at the nanometer scale, but approaches to expand the inorganic and electrical functionality of these scaffolds remain limited. Developments in nucleic acid metallics have enabled the incorporation of site‐specific metal ions in DNA duplexes and provide a means of functionalizing the double helix with atomistic precision. Here a class of 2D DNA nanostructures that incorporate the cytosine‐Ag+‐cytosine (dC:Ag+:dC) base pair as a chemical trigger for self‐assembly is described. It is demonstrated that Ag+‐functionalized DNA can undergo programmable assembly into large arrays and rings, and can be further coassembled with guanine tetraplexes (G4). It is shown that 2D DNA lattices can be assembled with a variety of embedded nanowires at tunable spacing. These results serve as a foundation for further development of self‐assembled, metalated DNA nanostructures, with potential for high‐precision DNA nanoelectronics with nanometer pitch.more » « less
