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 that
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 (
- NSF-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
-
more » « less
Abstract γ ‐modified peptide nucleic acids (γ PNAs) could be used to enable formation of complex, self‐assembling nanofibers in select polar aprotic organic solvent mixtures. Here we demonstrate that distinctγ PNA 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 ofγ PNA nanofibers, thereby overcoming a key hurdle for future scale‐up of applications related to nanofiber growth and micropatterning. -
more » « less
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 Oligonucleic acids (ONAs), such as DNA and RNA, are used in various biotechnology and nanotechnology applications due to their ability to form a double helix that is stable at low temperature and melts at high temperatures. The melting temperature (
T m) of ONA duplexes can be tuned by the ONA composition, sequence, length and concentration, solvent quality, and salt concentration and by conjugation to other macromolecules. In this article, we use coarse‐grained (CG) molecular simulations to study ONAs conjugated with linear homopolymers that are relatively more solvophobic than the ONA. We study charged and stiff 8‐mer ONAs (e.g., DNA) and neutral and flexible 8‐mer ONAs (e.g., peptide nucleic acids or PNA), and vary the composition (or G‐C content) and sequence of ONA, conjugated homopolymer lengths and solvent quality for the polymer. For neutral and flexible ONAs, as the solvent quality worsens for the polymer, the ONA melting temperature increases from that of unconjugated ONA. The melting curves broaden with polymer length and worsening solvent quality, especially for ONAs with higher G‐C content. For charged and stiff ONAs, as the solvent quality worsens, the ONA melting temperature decreases compared to unconjugated ONA while the width of the melting curve remains the same. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.2019 ,57 , 1196–1208 -
more » « less
Abstract Peptide nucleic acids (PNAs) are nucleic acid analogs with hybridization properties and enzymatic stability superior to that of DNA. In addition to gene targeting applications, PNAs have garnered significant attention as bio‐polymers due to the Watson–Crick‐based molecular recognition and flexibility of synthesis. Here, PNA amphiphiles are engineered using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γ PNA) amphiphiles self‐assemble into spherical vesicles. Further, nano‐assemblies (NA) are formulated using the amphiphilic γ PNA as a polymer via ethanol injection‐based protocols. Comprehensive head‐on comparison of the physicochemical and cellular uptake properties of PNA derived self‐ and NA is performed. Small‐angle neutron and X‐ray scattering analysis reveal ellipsoidal morphology of γ PNA NA that results in superior cellular delivery compate to the spherical self‐assembly. Next, the functional activities of γ PNA self‐and NA in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis‐based assays are compared. Overall, it is established that γ PNA amphiphile is a functionally active bio‐polymer to formulate NA for a wide range of biomedical applications.
-
more » « less
Abstract Monolayers of chiral molecules can preferentially transmit electrons with a specific spin orientation, introducing chiral molecules as efficient spin filters. This phenomenon is established as chirality‐induced spin selectivity (CISS) and was demonstrated directly for the first time in self‐assembled monolayers (SAMs) of double‐stranded DNA (dsDNA)1. Here, we discuss SAMs of double‐stranded peptide nucleic acid (dsPNA) as a system which allows for systematic investigations of the influence of various molecular properties on CISS. In photoemission studies, SAMs of chiral, γ‐modified PNA show significant spin filtering of up to
P = (24.4 ± 4.3)% spin polarization. The polarization values found in PNA lacking chiral monomers are considerably lower at aboutP = 12%. The results confirm that the preferred spin orientation is directly linked to the molecular handedness and indicate that the spin filtering capacity of the dsPNA helices might be enhanced by introduction of chiral centers in the constituting peptide monomers.
