Creating de novo peptide-based bioactivities: from assembly to origami

DNA origami has created complex structures of various spatial dimensions. However, their versatility in terms of function is limited due to the lower number of the intrinsic building blocks, i.e. nucleotides, compared with the number of amino acids. Therefore, protein origami has been proposed and demonstrated to precisely fabricate artificial functional nanostructures. Despite their hierarchical folded structures, chain-like peptides and DNA share obvious similarities in both structures and properties, especially in terms of chain hybridization; therefore, replacing DNA with peptides to create bioactivities not only has high theoretical feasibility but also provides a new bottom-up synthetic strategy. However, designing functionalities with tens to hundreds of peptide chains using the similar principle of DNA origami has not been reported, although the origami strategy holds great potential to generate more complex bioactivities. In this perspective review, we have reviewed the recent progress in and highlighted the advantages of peptide assembly and origami on the orientation of artificially created bioactivities. With the great potential of peptide origami, we appeal to develop user-friendly softwares in combination with artificial intelligence.