Universiteit Leiden

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Research project

Self-assembly properties and applications of metal-binding peptides and proteins

It is estimated that approximately 30% of all proteins require a metal to function. Investigating the relationship between metal-binding and peptide/protein folding allows us to uncover fundamental rules for creating metallo-peptides and proteins, which in turn leads to the creation of new structures, potentially with novel functions. Currently, Aimee Boyle focuses on three interrelated research projects with the aim of creating new structures that can fulfil a variety of different applications.

Aimee Boyle

Understanding metal-binding selectivity

In this project, helical scaffolds (for an example, see Figure 1) are employed to investigate why some metals bind to certain peptides and proteins, but not to others. Factors such as peptide stability, and the composition and position of the binding site are investigated. Using the information gained, new peptides that are selective for a particular metal will be synthesised and analysed. 

Figure 1. One of the peptide scaffolds used to probe metal-binding selectivity. This particular scaffold binds three metal ions (A) Side-view of the metallopeptide; (B) top-down view, and; (C) a close-up of the metal-binding site.

Creating peptides and proteins for biosensing applications

A crucial feature of biosensors is that they are specific for a particular molecule of interest. In this project, proteins will be engineered based on existing peptide designs. The initial challenge is to create the protein structures: the peptides need to be reengineered so that their helices are in an antiparallel (as opposed to parallel) orientation, and loops that join the helices together need to be created. Metal-binding sites then need to be inserted. The ultimate goal of these proteins is to modify them so they will bind only one type of metal ion: this specificity will be engineered using a combination of chemical and biological techniques. Such protein-based metal biosensors could have applications in detecting contaminants in water or soil for example.

Figure 2. Strategy for engineering metalloproteins from metal-binding peptide scaffolds.

Metal-containing hydrogels as antibacterial agents

Some metals have inherent antibacterial properties, making them useful for inhibiting bacterial growth in vivo. In this project, metal-containing hydrogels in which the metal is necessary for hydrogel formation will be designed, synthesised, and characterised with a view to exploring their application as antibacterial coatings for medical implants.

Figure 3. Transmission electron microscopy (TEM) images of hydrogel-forming metallopeptides. These images were taken during the gelation process and show that fibres grow and bundle together, leading to gelation.
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