Understanding Assembly Enables the Better Design of Peptide Conjugate Which May Form Useful and Functional Nanostructures

One of the most facile and versatile approaches for creating artificial dynamic biomaterials lies in the stimulus responsive strategies, in which structurally tunable moieties are conventionally incorporated. Peptides, which consist of the identical structural constituents with proteins, that is, amino acids, have been considered as one of the ideal synthetic building blocks to create stimulus-responsive biomaterials due to their remarkable biocompatibility and the intrinsic sequence-assembly relationship. The struc-tural tunability of natural or non-natural amino acids in hydrophobicity and conformation allows for precisely encoding the sequence of peptides, thus endowing a considerable number of the probability to modulate peptide self-assembly by utilizing biologically external or internal stimuli. Prion are a sin-gular subset of proteins able to switch between a soluble conformation and an amyloid state. The abil-ity to transit between these two conformations is encoded in the so-called “prion domains” which are long and disordered regions of low complexity, enriched in polar and uncharged amino acids. The po-lar nature of prion domains results in slow amyloid formation, which allow kinetic control of fiber as-sembly. To identify new ordered secondary structures here we report about synthesis and conforma-tional analysis of prion-inspired heptapeptides that spontaneously self-assembling into highly ordered, non-toxic amyloid fibrils under physiological conditions. The peptides here presented are: i) synthetic homologues of natural, metabolically stable bioactive sequences and, therefore, able to form specific secondary structures; ii) composed of hydrophobic amino acid with specific non-covalent interactions (hydrogen bonds, hydrophobic interactions); iii) used as building blocks to build oligopeptides which assume new, regular secondary structure.