Self-Assembled Nanomaterials Based on Beta (β3) Tetrapeptides

Abstract

β 3-amino acid based polypeptides offer a unique starting material for the design of self-assembled nanostructures such as fibres and hierarchical dendritic assemblies, due to their well-defined helical geometry in which the peptide side chains align at 120° due to the 3.0–3.1 residue pitch of the helix. In a previous work we have described the head-to-tail self-assembly of N-terminal acetylated β 3-peptides into infinite helical nanorods that was achieved by designing a bioinspired supramolecular self-assembly motif. Here we describe the effect of consecutively more polar side chains on the self-assembly characteristics of β 3-tetrapeptides Ac-β 3Ala-β 3Leu-β 3Ile-β 3Ala (Ac-β3[ALIA]), Ac-β3Ser-β 3Leu-β 3Ile-β 3Ala (Ac-β3[SLIA]) and Ac-β 3Lys-β 3Leu-β 3Ile-β 3Glu (Ac-β3[KLIE]). β 3-tetrapeptides complete 1 1/3 turns of the helix: thus in the oligomeric form the side chain positions shift 120° with each added monomer, forming a regular periodic pattern along the nanorod. Dynamic light scattering (DLS) measurements confirmed that these peptides self-assemble even in highly polar solvents such as water and DMSO, while diffusion-ordered NMR spectroscopy revealed the presence of a substantial monomeric population. Temperature dependence of the size distribution in DLS measurements suggests a dynamic equilibrium between monomers and oligomers. Solution casting produced distinct fibrillar deposits after evaporating the solvent. In the case of the apolar Ac-β 3[ALIA] the longitudinal helix morphology gives rise to geometrically defined (~70°) junctions between fibres, forming a mesh that opens up possibilities for applications e.g. in tissue scaffolding. The deposits of polar Ac-β 3[SLIA] and Ac-β 3[KLIE] exhibit fibres in regular parallel alignment over surface areas in the order of 10 μm.