PNA Molecular Self-Assembly

Currently, the application of peptide nucleic acids is mainly in the field of gene expression, and PNAs are much later to be used in nanotechnology. PNAs have the specific base-pair recognition properties of DNA and the material-like properties of polyamides, which allow relatively simple modification and conjugation of various chemical groups to the peptide backbone. PNAs are capable of sharing the specific molecular recognition through the precise Watson-Crick base pairing, and thus have potential for nanotechnology based on the self-assembly of PNA structures.

Fig 1. Schematic illustrations of the four main approaches to molecular self-assembly using PNA. (Berger, O.; E. Gazit. 2017)

Our PNA Molecular Self-Assembly Technologies

At BOC Sciences, our experts are able to design and synthesize a series of supramolecular assemblies based on nano-PNA with well-organized structures and nanostructure engineering applications by combining the unique structure of DNA with the chemical versatility of peptides.

• Synthesis of PNA Amphiphiles

PNA is able to form PNA amphiphiles with other substances, resulting in lipid-integrated structures, hydrogels or fibrillary assemblies. We have designed the synthesis of different PNA sequences linked to alkanes of different lengths.

• Firstly, the PNA is incorporated in phospholipid liposomes by their conjugation to a synthetic di-alkyl lipid tail.
• Then, we add naturally charged amino acids and spacers composed of glycines to the sequence, these modifications result in stable liposomes that present the PNA domains and therefore bind complementary DNA chains.
• As a result, PNA amphiphiles have been shown to detect single stranded PCR products of different lengths, providing a novel method for gel-free DNA analysis.

• Synthesis of PNA-peptide amphiphiles conjugates

We can also couple a specific PNA segment to a peptide sequence to generate nanofibers, and PNA-peptide amphiphiles conjugates can self-assemble into nanofibers and bind to oligonucleotides with high affinity and specificity. These obtained fibers are highly attractive for nucleic acid purification and biosensors.

• Preparation of PNA-based Amphiphilic Polymer Brushes

Single-stranded PNA sequences are formulated into high-density brushes by graft-through polymerization using ring-opening complex polymerization (ROMP) method. PNA-based amphiphilic polymer brushes can be applied for nucleic acid delivery to cells and DNA purification.

• Synthesis of PNA-DNA Duplexes

Compared to DNA, heterologous double-stranded DNA-PNA has higher stability. Our experts can also insert PNA molecules into a series of self-assembling DNA building blocks to obtain the self-assembly of PNAs into nanoparticles, thereby improving the chemical and thermal stability of DNA.

• The PNA is incorporated into a DNA double crossover (DX) molecule to obtain a hetero-duplex.
• Then, targeting a dimeric G-quadruplex telomeric sequence with a G-rich PNA probe to obtain hetero-quadruplex.
• Finally, biological DNA-based G-quadruplexes are formed.

• Minimalistic PNA

Both guanine-containing di-PNA assemblies and guanine-PNA monomer spheres display unique optical properties. di-PNA is the shortest PNA building block that can self-organize into an ordered structure, allowing us to obtain self-assembly of guanine-based PNA molecules without other additives.

• Modification of PNA Assembly by Small Molecules

The co-assembly of PNA with thymidine-like trihedral cyanuric acid allows polyadenine PNA to assemble into fibers. We also present a novel strategy of PNA self-assembly using a small molecule with three thymine-like facets to modify the structure of polyadenine nucleic acid.

Cyanuric acid is added to hepta-adenine PNAs, and the assembly process is monitored by UV spectrum. These micrometer-long fibers can be produced in large quantities and the composition is cheap and non-toxic.

Fig 2. Self-Assembly of PNA-Photosensitizer Conjugates. (Chang, R.; et al. 2020)

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