Design rules for de novo self-assembling peptide nanostructures

Self-assembling peptides represent a versatile chemical toolbox for the development of discrete nanostructures that can be tailored for a variety of biomedical applications. Rational design of a peptide building block involves wise selection from the amino acids pool to create a primary sequence capable of adopting a bioinspired secondary structure stabilized by a combination of non-covalent and/or covalent interactions in response to external stimuli. Herein, we focus on the basic molecular design rules for self-assembling peptides as the building units for supramolecular nanomaterials formation through a bioinspired bottom-up design strategy. We look at the physicochemical nature of different amino acids and their proposed sequence arrangements needed to guide the molecular assembly into higher-order structures governed by certain types of intra- and/or intermolecular interactions and to give insights into how the materials’ structural and functional properties can be fine-tuned to satisfy different application needs. We will discuss the structural features of biosynthesized protein nanomaterials (such as collagen, elastin-like, silk-elastin-like, keratin, and resilin) and how they inspired the development of mimetic self-assembling polypeptide analogues of shorter length, while keeping the inherent material properties of the parent designs. In addition, design rules of de novo short peptides which assemble into higher bioinspired structures (β-sheets, β-hairpins, α-helices and amphiphiles assembly), as well as unconventional peptide designs (short aromatic and cyclic peptides), are also explained. This is an introductory chapter that gives a comprehensive overview of the basic design rules for the main classes of self-assembling peptides, which are discussed in more details in the relevant chapter for each class.