Molecular self-assembly using peptide nucleic acids

Abstract

Peptide nucleic acids (PNAs) are extensively studied for the control of genetic expression since their design in the 1990s. However, the application of PNAs in nanotechnology is much more recent. PNAs share the specific base-pair recognition characteristic of DNA together with material-like properties of polyamides, both proteins and synthetic polymers, such as Kevlar and Nylon. The first application of PNA was in the form of PNA-amphiphiles, resulting in the formation of either lipid integrated structures, hydrogels or fibrillary assemblies. Heteroduplex DNA-PNA assemblies allow the formation of hybrid structures with higher stability as compared with pure DNA. A systematic screen for minimal PNA building blocks resulted in the identification of guanine-containing di-PNA assemblies and protected guanine-PNA monomer spheres showing unique optical properties. Finally, the co-assembly of PNA with thymine-like three-faced cyanuric acid allowed the assembly of poly-adenine PNA into fibers. In summary, we believe that PNAs represent a new and important family of building blocks which converges the advantages of both DNA- and peptide-nanotechnologies.

Figure 1

Representative chemical structures of peptide, DNA, and PNA. The side-chains which can be replaced by any amino acid residue in peptides, or nucleobase in the case of DNA and PNA, are highlighted in red

Figure 2

Schematic illustrations of the four main approaches to molecular self-assembly using PNA. (A) A PNA amphiphile is composed of a PNA strand (red) conjugated to a hydrophobic domain (yellow). When assembled in solution nanostructures such as spheres or fibers with a hydrophobic core are formed and the PNA are displayed on their surface in high density. (B) PNA can bind complementary sequences of DNA to form hybrid duplexes. These hybrids can then be used to generate typical nucleic acid assemblies such as G-quadruplex, or more elaborated designs using structural DNA nanotechnology methods. (C) PNA molecules as short as di-PNAs, have been shown to assemble through a combination of Watson–Crick interactions and aromatic stacking into different nanostructures with unique physical properties. (D) The co-assembly of PNA with cyanuric acid, a small molecule exhibiting three thymine-like faces, allows the organization of poly-adenine PNA into fibers