My research focuses on design of peptide antagonists with high affinity and specificity for inhibiting protein-protein interactions. While forces driving stability are now well understood, much less is known about designing specificity. We use a Protein-fragment Complementation Assay (PCA), which utilises semi-rational design to select antagonists of Jun and Fos peptides that interact in the oncogenic Activator Protein-1 transcriptional regulator. We have 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 coiled coil stability and specificity based only the primary sequence, and to consequently design peptides. Our screening approach is also applied to a range of other therapeutically relevant systems that include β-amyloid and α-synuclein 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.