Our research focuses on the design of peptide antagonists that can inhibit disease-relavant targets with high affinity and specificity by inhibit the protein-protein interactions (PPIs) that they require for function. While forces driving stability are now well understood, much less is understood about specificity. We use a Protein-fragment Complementation Assay (PCA), which utilises semi-rational design to select peptide antagonists. We have further devised a Competitive and Negative Design Initiative (CANDI) technique to increase target-specificity in the PCA system by expressing potential off-targets during selection. Peptides generated have allowed us to predict PPI stability and specificity based on primary sequence, and to consequently design inhibitory peptides. Our screening approach has been applied to a broad range of other therapeutically relevant systems that include signalling proteins, transcription afctors, and the amyloidogenic proteins β-amyloid and α-synuclein that are implicated in the pathogenesis of Alzheimer’s and Parkinson’s diseases, respectively.

Ongoing projects related to the design and characterisation of peptide-based inhibitors of proteins involved in disease.