β-peptides

The need for new materials that meet the continuously changing industries led scientists to search for a new non-conventional materials. One of the newly developed materials is the so-called smart materials. Smart materials possess inherent functionality and ability to respond to different environmental stimuli. Those materials of interest are used in different applications such as; optical biosensors, molecular electronics, and regenerative medicine (Scanlon, 2008). The functionality of smart materials can be achieved by designing a functional hierarchical structure using the self-assembly. In building the hierarchical structure, small building units with a specific chemical or physical responses are allowed to grow on a surface or in solution –bottom-up-self-assembly (Fairman, n.d.). The small building units referred to – nanostructures – are designed in a manner that growing the materials does not affect the functionality of the nanostructure. Thus, the self-assembly process would result in large scale materials that inherited the characteristics of the small nanostructure units.

In the self-assembly process, well-ordered structures are held together via non-covalent bonds (Zhang, 1999). A major problem in developing the self-assembly technique is the fact that the non-covalent interactions are non-specific interactions. It is hard to grow large structures using that technique due to the side interactions. If developed more specific interactions well-ordered hierarchical structures will be obtained. The primary key in preventing side interactions and growing well-ordered structures is using strong non-covalent interactions such as hydrogen bond to overcome any weaker side interactions (Seoudi, 2016).

Peptide-based bio-inspired materials are materials that can be designed and synthesized using the technique bottom-up-self-assembly. For the two types of peptides alpha and beta, the N-H of the amide group and the O-H of the carboxyl group can act as a bridge for growing well-ordered peptide structures within the same sequence. 14-helix peptides are a type of beta-peptides designed where intramolecular hydrogen bond occurs between the carbonyl oxygen of the amide group of residue i and N-H of the amide group of residue i+2, for that only three peptide residues are required to form a complete turn. Recently, one implemented structure was developed (Seoudi, 2015) where one end of the beta peptide is acetylated. The acylation of one end allows for the formation of intermolecular hydrogen bond between the different units. Importantly, this small modification also copies the intramolecular hydrogen bonding motif to the termini, offering three hydrogen bond donors at the C-terminus and three hydrogen bond acceptors at the N-terminus. The self-assembly happens by stack monomers – head-to-tail– above each other and the building units grow in a controlled manner, the formation of fibers and fibers bundles for up to few millimeters in length were reported using this motif (Seoudi, 2015). The resulted structures are so-called supermolecular nano-structures fold into a helix in the aqueous medium which is of great importance because most biomedical applications are performed in aqueous solution. The major challenge in the development of 14-helix nanostructure is the same hydrogen bond motif that the 14-helix peptides adopt. In aqueous solution, the folding of the peptide can be disturbed due to hydrogen bond competition of the solvent (water) on the peptides sites allowing for the self-assembly structures to be observed only upon solvent vaporization.

A possible way to avoid this problem is the insertion of cyclic constrained backbone to stabilize the helix in aqueous medium. Yet, the insertion of cyclic constrained backbone lowers the peptide solubility and less functionality would be possible. Although at least five of seven residues have to be constrained for β-peptide to adopt a 12-helix conformation in water (DeGrado, 1999), it is predicted that 14-helix can fold into a stable helix with less constrained side chain number due to the alignment of the side chain. Thus more studies are needed to design and discover the effect constrained side chains on the acetylate beta peptides.
By: 
Dr. Rania S. Seoudi

References:

DeGrado, W. S. J. a. H. Y., 1999. The twists and turns of β‐peptides. The Journal of peptide research, 54(3), pp. 206-217.

Fairman, R. a. Å. K., n.d. Peptides as novel smart materials. Current Opinion in Structural Biology, Volume 15, pp. 453-463.

Scanlon, S. a. A. A., 2008. A. Self-assembling peptide nanotubes. Nano Today, Volume 3, pp. 22-30.

Seoudi, R. D. B. M. K. K. P. P. A. M. a. M. A., 2015. Supramolecular self-assembly of 14-helical nanorods with tunable linear and dendritic hierarchical morphologies. New Journal of Chemistry, 39(5), pp. 3280-3287.

Seoudi, R. H. M. W. D. A. C. D. B. M. A. M. P. P. a. M. A., 2016. Self-assembled nanomaterials based on beta (β 3) tetrapeptides. Nanotechnology, 27(13).

Zhang, S. a. A. M., 1999. Peptide self-assembly in functional polymer science and engineering. Reactive and Functional Polymers, 41(1-3), pp. 91-102.