<p>Peptides are a fundamental building-block of living systems and play crucial roles at both functional and structural level. Therefore, they have attracted increased attention as a platform to design and engineer new self-assembled systems that span the nano-to-meso scales. The rules of peptide design and folding enable the construction of suitable building-blocks to develop soft materials for biomaterial applications. Herein we present the use of the alpha-helical secondary structure to create two distinct structural motifs, namely coiled-coils and helical bundles. These peptide components can differ in size and incorporate a host of different functional moieties, the effects of which are described through their hierarchical assembly. </p>
<p>First, we describe the self-assembly of coiled coil oligomers (trimer and tetramer) of the GCN4 leucine zipper peptide. The trimeric coiled coil was modified with varying number of aromatic groups (one to three) along each helical backbone, to facilitate higher order assemblies into banded nano- to micron-sized structures, the formation of which could be controlled reversibly as a function of pH. In addition, the electrostatic and aromatic interactions of the peptide material were harnessed for non-covalent binding of small drug molecules, followed by their subsequent pH-triggered release. Furthermore, these nanostructures are compatible with MCF-7 breast cancer cells, making them suitable drug-delivery agents for chemotherapeutics. In the absence of aromatic modifications, the coiled-coil trimer assembles into higher-order nanotubes that can be harnessed for selective encapsulation of high molecular weight biomolecules. With an increase in oligomerization from three to four, along with a single aromatic group modification on each helix, the tetrameric coiled-coil mutant successfully demonstrates a metal-assisted two-tier structural assembly into microbarrels and spheres.</p>
<p>Second, we present the higher-order assembly of short tetrameric and pentameric helical bundle proteins, covalently stabilized by a belt of disulfide bridges, with metal-binding ligands at each helix termini. The addition of metals like Zn(II) and Cu(II) promote the assembly of the bundles into a 3D globular matrix, which upon thermal annealing transforms into microspheres. Additionally, these microspheres also demonstrate the metal-assisted inclusion of His-tagged fluorophores. Thus, peptide-based materials can be constructed by self-assembly of alpha-helical building blocks into systems with sophisticated, diverse morphologies and dynamic chemical properties, that can be further modulated to enhance performance for medical applications. </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/9904796 |
| Date | 17 October 2019 |
| Creators | Monessha Nambiar (7430762) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Exploring_Higher-Order_Alpha-Helical_Peptide_Assemblies_for_Biomaterial_Applications/9904796 |
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