Electrospinning is a well-known, straightforward, and versatile technique, widely used for the preparation of fibers by electrifying a polymer solution. However, a high molecular weight is not essential for obtaining uniform electrospun fibers; in fact, the primary criterion to succeed is the presence of sufficient intermolecular interactions, which function similar to chain entanglements. Some small molecules able to self-assemble have been electrospun from solution into fibers and, among them, peptides containing both natural and non-natural amino acids are of particular relevance. Nowadays, the use of peptides for this purpose is at an early stage, but it is gaining more and more interest, and we are now witnessing the transition from basic research towards applications. Considering the novelty in the relevant processing, the aim of this review is to analyze the state of the art from the early 2000s on. Moreover, advantages and drawbacks in using peptides as the main or sole component for generating electrospun nanofibers will be discussed. Characterization techniques that are specifically targeted to the produced peptide fibers are presented.

The development of molecular carriers able to carry molecules directly into the cell is an area of intensive research. Cationic nanoparticles are effective delivery systems for several classes of molecules, such as anticancer agents, oligonucleotides and antibodies. Indeed, a cationic charge on the outer surface allows a rapid cellular uptake together with the possibility of carrying negatively charged molecules. In this work, we studied the self-assembly of an ultra-short ααβ-tripeptide containing an L-Arg–L-Ala sequence and an unnatural fluorine substituted β^2,3-diaryl-amino acid. The presence of the unnatural β^2,3-diaryl-amino acid allowed us to obtain a protease stable sequence. Furthermore, an arginine guanidinium group triggered the formation of spherical assemblies that were able to load small molecules and enter cells. These spherical architectures, thus, represent interesting candidates for the delivery of exogenous entities directly into cells.

Rac1 GTPase interaction with guanine nucleotide exchange factor Tiam1 is involved in several cancer types and cardiovascular diseases. Although small molecules interfering with their protein‐protein interaction (PPI) were identified and studied, the ability of small peptides and peptide mimics acting as Rac1/Tiam1 PPI inhibitors has not been yet explored. Using computational alanine scanning (CAS), the “hot” interfacial residues have been determined allowing the design of a small library of putative PPI inhibitors. In particular, the insertion of an unnatural alpha, alpha disubstituted amino acid, that is norbornane amino acid, and the side chain stapling have been evaluated regarding both conformational stability and biological activity. REMD calculations and CD studies have indicated that one single norbornane amino acid at the N‐terminus is not sufficient to stabilize the helix structure, while the side‐chain stapling is a more efficient strategy. Furthermore, both engineered peptides have been found able to reduce Rac1‐GTP levels in cultured human smooth muscle cells, while wild type sequence is not active.