Molecular basis for the changes in the assembly structures of bioactive peptides.

Peptide supramolecular assemblies can compete with designed proteins in their capacity to offer useful biological functions and structural diversity to synthetic soft matter. Besides the extensive use of peptidic sequences to mimic the functional domains of large proteins, the ability to program a vast array of structures through changes in sequences via straightforward solid-phase synthesis has led to the use of peptides as self-assembling building blocks. In particular, the combination of bioactive and self-assembling epitopes generates customized nanomaterials for various biomedical applications. This potential is particularly interesting given the possibility of integrating multiple biological functionalities into a supramolecular scaffold of peptides. From structural perspective peptide assemblies can generate filaments, 2D-sheets, spheres, networks, helices and more complex shapes that will no doubt be discovered in the future as we learn to master morphogenesis of peptide assemblies. Here we focus on a peptidic system composed composed by a short multifunctional peptide linked to a hydrophobic peptide sequence. The hydrophobic sequence can be designed to form β-sheets among the hydrophobic side chains, while the residue farthest from the tail are the multifunctional sequence and, in some cases, promote solubility. In water β-sheet formation and collapse of the hydrophobic sequence induce assembly of the molecules into supramolecular, one-dimensional nanostructures. These nanostructures hold significant promise for biomedical functions due to their ability to display a high density of biological signals on their surface for targeting or to activate pathways, as well as for biocompatibility and biodegradable nature. Recent studies show that selectivity and potency of self-assembled bioactive peptides are affected in relation to transport system used. The future success of bioactive self-assembling nanostructures in biomedical applications strongly depends on the ability to fine-tune the density and display of bioactive epitopes- creating more complex heterovalent structures- while nor interfering whit the self-assembly process. Therefore, the development of bioactive self assembling structures is strongly coupled to a detailed understanding of the self-assembling properties of the systems, its dynamic and its susceptibility to change. This work aims to highlight the diversity of self-assembled nanostructures constructed from mono-dispersed synthetic building blocks, with a particular focus on their design, self-assembly, functionalization with bioactive ligands and effects thereof on the self-assembly, and possible applications.