The development of conformationally constrained analogues of bioactive peptides is a relevant goal in peptide medicinal chemistry. Among the several classes of conformationally constrained peptides, the so‐called stapled peptides, which bear a side‐chain‐to‐side‐chain bridge, are particularly interesting since they offer the possibility to stabilize specific conformational elements, such as α‐helices or β‐turns. We describe an efficient and reproducible microwave‐assisted strategy to prepare side‐chain‐to‐side‐chain clicked peptides, performing the copper‐catalyzed azide‐alkyne cycloaddition on solid phase, using as a model peptide a portion of the H1‐relaxin B chain, which contains the binding cassette motif of this important bioactive peptide. All the relevant parameters, that is, resin, solvent, catalytic system, microwave energy and reaction time were optimized using a systematic one‐factor‐at‐a‐time (OFAT) approach. This method will be useful for the preparation of libraries of conformationally constrained relaxin analogues.

Poor colloidal stability of gold nanoparticles (AuNPs) in physiological environments remains one of the major limitations that contribute to their difficult translation from bench to clinic. For this reason, an active research field is the development of molecules able to hamper AuNPs aggregation tendency in physiological environments. In this context, synthetic peptides are gaining an increased interest as an alternative to the use of biomacromolecules and polymers, due to their easiness of synthesis and their profitable pharmacokinetic profile. In this work, we reported on the use of ultrashort peptides containing conformationally constrained amino acids (AAs) for the stabilization of AuNPs. A small library of non-natural self-assembled oligopeptides were synthesized and used to functionalize spherical AuNPs of 20 nm diameter, via the ligand exchange method. The aim was to investigate the role of the constrained AA, the anchor point (at C- or N-terminus) and the peptide length on their potential use as gold binding motif. Ultrashort Aib containing peptides were identified as effective tools for AuNPs colloidal stabilization. Furthermore, peptide coated AuNPs were found to be storable as powders without losing the stabilization properties once re-dispersed in water. Finally, the possibility to exploit the developed systems for binding proteins via molecular recognition was also evaluated using biotin as model.

Aggregation-induced emissive materials are gaining particular attention in the last decades due to their wide application in different fields, from optical devices to biomedicine. In this work, compounds having these kinds of properties, composed of tetraphenylethylene scaffold combined with fatty acids of different lengths, were synthesized and characterized. These molecules were found able to self-assemble into different supramolecular emissive structures depending on the chemical composition and water content. Furthermore, they were used as N-terminus capping agents in the development of peptide-based materials. The functionalization of a 5-mer laminin-derived peptide led to the obtainment of luminescent fibrillary materials that were not cytotoxic and were able to form supramolecular gels in aqueous environment.