Exploring Artificial Nucleic Acid Mimicking Peptide Nanofibers

• Published in: Chemistry of materials Vol. 35; no. 11; pp. 4355 - 4365
• Main Authors: Hendrikse, Simone I. S., Todorova, Nevena, Soleimaninejad, Hamid, Charchar, Patrick, Sani, Marc-Antoine, Al Taief, Karrar, Berengut, Jonathan F., Wickham, Shelley F. J., Gras, Sally L., Fahrenbach, Albert C., Thordarson, Pall, Ellis, Amanda V.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 13.06.2023
• ISSN: 0897-4756; 1520-5002
• DOI: 10.1021/acs.chemmater.3c00445

Nucleic acids play key roles in Nature, including storage of genetic information and translation into a wide variety of proteins that collectively build up cells. Their intrinsic programmability can be utilized to bind specific targets for a wide variety of biomedical applications. However, naturally derived nucleic acids are susceptible to degradation and their large-scale synthesis is costly. Although artificial polymeric nucleic acids show great promise, they are typically more flexible, and therefore their secondary structure is hard to control. Here, we designed polymerizable monomers that upon free-radical polymerization were able to form micrometer-long fibrous structures containing mononucleotide grafts. These fibers were a direct result of predesigned noncovalent interactions along the polymer backbone supported by the inclusion of peptide linkers installed between polymerizable headgroups and mononucleotides. The resulting hybrid nucleic acid-peptide homopolymers exhibited secondary structure signatures analogous to natural RNA but were unfolded and fibrous in morphology, in contrast to the collapsed globular structures typically observed for natural RNA in water. The peripheral exposed mononucleotides showed capacity to engage in complementary binding, albeit weak, to both one-dimensional (1D) and more complex three-dimensional (3D) nucleic acid structures, showing potential to be utilized as templates for biomedical applications.