Exploring Artificial Nucleic Acid Mimicking Peptide Nanofibers

Nucleic acids play key roles in Nature, including storageof geneticinformation and translation into a wide variety of proteins that collectivelybuild up cells. Their intrinsic programmability can be utilized tobind specific targets for a wide variety of biomedical applications.However, naturally derived nucleic acids are susceptible to degradationand their large-scale synthesis is costly. Although artificial polymericnucleic 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 polymerizationwere able to form micrometer-long fibrous structures containing mononucleotidegrafts. These fibers were a direct result of predesigned noncovalentinteractions along the polymer backbone supported by the inclusionof peptide linkers installed between polymerizable headgroups andmononucleotides. The resulting hybrid nucleic acid-peptide homopolymersexhibited secondary structure signatures analogous to natural RNAbut were unfolded and fibrous in morphology, in contrast to the collapsedglobular structures typically observed for natural RNA in water. Theperipheral exposed mononucleotides showed capacity to engage in complementarybinding, albeit weak, to both one-dimensional (1D) and more complexthree-dimensional (3D) nucleic acid structures, showing potentialto be utilized as templates for biomedical applications.