Spherical shape supramolecular structure of serum stable self- assembled pentapeptides containing the constrained norbornene amino acid

Self-assembly is a spontaneous process by which unordered systems of monomers organize into ordered structures as the result of non-covalent interactions and lies behind a number of biological nanostructures. Supramolecular spontaneous assembly of high molecular weight peptides or peptides conjugated with non-peptidic molecules has been reported. Less is known on the self-assembly of short peptides alone which self-organize predominantly into nanotubes and nanofibers. Spherical (micellar and vesicle-like) architectures are rarely described although they appear very attractive, due to promising applications in biomedicine and nanotechnology. Besides the numerous advantages of using peptides containing natural amino acids for nanostructures, they present some limitations such as low bio-stability and unstable conformation especially when they are short or medium-sized. The insertion of unnatural amino acids in the peptide sequences is a well-known tool to overcome these problems.

Here we report on the preparation and self-assembly of short hydrophobic peptides able to stabilize the formation of supramolecular spherical shape assemblies in water. Two diastereoisomeric pentapeptides AcAla-NRB-Ala-Aib-AlaNH2 1 and 2, containing the unnatural constrained norbornene amino acid (NRB) 3, were prepared. Interestingly, peptides 1 and 2 are insoluble in organic solvents but completely soluble in water despite the presence of hydrophobic non polar norbornene scaffold. An interesting feature of these peptides is also the presence of the C-C double bond in the norbornene scaffold, which could allow the easy labelling of the system introducing a variety of useful biotag. DLS Analysis, Conformational studies, Serum stability was performed and reported.