Functional Assemblies Based on Novel Nucleic Acid–Peptide Chimeras

Agata Chotera agatachotera@gmail.com Gonen Ashkenasy
Chemistry Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Biological systems, where weak non-covalent interactions of simple building blocks form functional complex machinery, gave rise to biologically inspired self-assembling materials, based for example on peptides and nucleic acids. Although self-organizing systems based on them have been explored in many aspects, artificially synthesized hybrid molecules are novel and exhibit noticeable importance in material science and biomedical research. The topic of our research is the emergence of a primitive synergy in assemblies of simple nucleic acid – peptide chimeras. In our system, two short complementary DNA segments are attached to amphiphilic peptide sequences previously investigated in our lab1-3. We show that conjugation of short peptide and nucleic acid segments, and spontaneous assembly of the product conjugates, can yield new structures based on both the peptide association and sequence-specific hybridization of the oligonucleotides. We demonstrate the self-assembly of our system into different morphologies: fibers and spherical structures and we present the co-assembly pathway leading from one type of aggregate to another. Furthermore, these assemblies are superior, in terms of structure stability and function, as compared to the non-conjugated peptide and nucleic-acid components. To the best of our knowledge, this study proposes the first systematic analysis of structural and functional characteristics of small double stranded peptide-oligonucleotide conjugates4. We believe that these or similar molecules could serve in the future as new materials for various applications, such as catalysis, electron transfer and drug delivery. Additionally, studying such conjugates may shed light on bottom-up scenarios related to the origin of life, due to the possible co-evolution of protein and nucleic acids as replicating entities in the early chemical evolution.

Gradual structural changes along the chemical evolution driven by mixing amphiphilic peptides with increasing amounts of DNA-pep chimeras.

  1. B. Rubinov, N. Wagner, H. Rapaport and G. Ashkenasy, Angew Chem Int Ed Engl, 2009, 48, 6683-6686.
  2. B. Rubinov, N. Wagner, M. Matmor, O. Regev, N. Ashkenasy and G. Ashkenasy, ACS nano, 2012, 6, 7893-7901.
  3. M. Tena-Solsona, J. Nanda, S. Díaz-Oltra, A. Chotera, G. Ashkenasy, B. Escuder, Chem. Eur. J., 2016, 22, 6687-94.
  4. A. Chotera, R. Cohen-Luria, P.-A. Monnard, G. Ashkenasy (manuscript submitted for publication).








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