Peptide-DNA conjugates as building blocks for de novo design of hybrid nanostructures

Inspired by nature, modern nanotechnology has enabled the bottom-up construction of molecular machines and nanorobots using two different biomolecular building blocks, DNAs or peptides. As an emerging research field, synergizing these two biomolecular codes into a single nanostructure has provided super-powerful molecular tools into the arsenal of modern nanotechnology. Among them, peptide-DNA conjugates possess both attributes of peptide and DNA and can be arbitrarily predefined in given structural configurations, standing out as unique nanoscale building blocks for de novo design of instrumental nanostructures that otherwise could not be composed by using DNA or peptides only. Herein, the term peptide is used in the broadest sense, including oligopeptide, polypeptide, and protein. In this tutorial review, we survey the main progress made within the past decade in how to use peptide-DNA conjugates as nanoscale bricks to self-assemble hybrid nanostructures for different chemical and biological purposes. A concise perspective is included for existing challenges and potential future research directions. Looking to the horizon, peptide-DNA conjugates may serve as key structural elements in the coming decade to enable the bottom-up construction of advanced molecular machines, even comparable to those cellular organelles evolved by nature.