UNNATURAL AMINO ACIDS AS SYNTHETIC TOOLS FOR THE PREPARATION OF COMPLEX MOLECULAR ARCHITECTURES

Self-assembly is the process by which an organized structure spontaneously is formed from individual components, as a result of specific, local interactions between the units. In recent years, peptide-based self-assembled structures have emerged as a powerful approach for developing soft and hybrid materials due to their biocompatibility, biodegradability and easily tuning properties of the final structure. The introduction of non-natural amino acids into a peptide backbone imparts additional features such as reduced conformational flexibility, high tendency to adopt a well-defined secondary structure and enhanced metabolic stability. My PhD thesis is focused on the synthesis of ultrashort peptides containing non-natural scaffolds which are able to self-assemble and form supramolecular structures. The thesis is divided into three chapters, each one reports a project regarding the synthesis and chemical characterization of scaffolds which can be inserted in peptide sequences and exploited for developing soft or hybrid materials by self-assembly. The first chapter concerns the supramolecular assemblies of spherical shape obtained from different peptides containing Cα,α-tetrasubstituted amino acids. Firstly, the results on a pentapeptide containing norbornene amino acid is reported (work published on RSC Advances). Then, the simplification of this structure is reported until obtaining a pentapeptide containing Ala-Aib motif only. The ability of this peptide to form aggregates that can be exploited for the encapsulation of hydrophobic molecules has been studied. As a proof of concept the well-known curcumin molecule has been used. The interaction of the drug molecules with peptide aggregates has been studied using the absorption and the intrinsic fluorescence emission of curcumin. Starting from this peptide, it is also possible to develop peptide-ligands which stabilize gold nanoparticles in aqueous solution. The stability of nanoparticles has been studied using DLS and UV-vis spectroscopy. The second chapter reports on a β2,3-diarylamino acid, developed in our group, which is non-natural analogous of the dipeptide Phe-Phe. This amino acid has been used to develop hybrid antifouling film which has been characterized using different techniques (contact angles values, QCM-D). The third chapter concerns the preparation of an original heterocyclic scaffold to be inserted into a peptide backbone and its exploitation for the formation of soft materials by the way of an “induced assembly”. The electrospinning technique allowed the formation of electrospun nanofibers from these non-natural peptide-based small molecules and their characterization with several techniques (SEM, AFM, FT-IR, Raman) is reported.