New sample preparation and screening approaches will expand the range of targets that can be tackled by FBD

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The current limitation of FBD is the range of targets that are amenable to the approach. The majority of successful FBD programs have been conducted against soluble and relatively small (<50 kDa) protein domains.

Large proteins and membrane proteins provide significant challenges. These include preparation of the protein samples to be suitable for biophysical screening and circumventing technical issues such as protein stability, assay sensitivity and assay interference from additives that are required to maintain the protein in solution.

Our three academic institutes have each established significant resources for protein expression and purification. In collaboration with our industry partners, we will prepare samples of larger, more complex and membrane-bound proteins, such as G-protein coupled receptors (GPCRs) and ion channels. We will evaluate the applicability of our FBD approaches to these more challenging targets.

On-going projects:

• Enabling fragment-based lead discovery for challenging targets, such as ion channels and G-protein coupled receptors (GPCRs)
• Synthesis of aromatic ¹⁹F-¹³C TROSY-NMR probes to enable detailed study of the function and dynamics of biomolecular structures
• Develop membrane protein preparations for use on SPR chips