Tailored Materials for Protein Encapsulation and Stabilisation

Proteins are complex 3D assemblies made up of long chains of amino acids. Depending on the sequence of these amino acids, the 3-dimensional structure of the protein and its corresponding function differs. Proteins are identified by their biological roles within the body, varying from enzymatic duties to structural responsibilities.

Although proteins are capable of executing intricate and complex tasks on incredibly short timescales, they are often subject to denaturation outside of biological settings. This makes it difficult to investigate proteins and almost impossible to take advantage of the unique abilities they encompass.

This PhD project attempts to solve this ongoing stability problem associated with proteins through encapsulation and stabilisation within supramolecular frameworks. Encapsulation is promoted through favourable host-guest interactions, allowing us to then potentially study the protein and possibly exploit its functions for practical applications.

The magnitude of proteins makes it difficult to design a supramolecular architecture big enough to encapsulate them. Because of this, complete understanding of preferential binding motifs between proteins and supermolecules is important. This can be somewhat investigated by encapsulating smaller amino acids and peptides.

It is also possible to design supramolecular cages based biological structures. This can be accomplished through metal-ion mediated self-assembly of amino acids or peptides. This could be a starting point for designing a large enough framework that will preferentially exist as a host-guest complex upon introduction of a protein.

As demonstrated in Nature Communications, it is also possible to encapsulate a protein by tethering it covalently to a ligand.1 Upon addition of a metal ion and additional ligand, a self-assembled framework forms around the tethered protein. Identifying favourable interactions within this system can offer a design motif for encapsulation without the need for covalent attachment of the protein.