Our research is centred on developing chemical tools to understand and inhibit therapeutically significant protein-protein interactions. This work encompasses aspects of chemical biology, synthetic organic chemistry, peptide and protein chemistry, chemical proteomics and medicinal chemistry. The group is highly multidisciplinary in nature and we work in collaboration with groups at Imperial within Natural Science and Medicine and with other labs across the UK.
Protein-protein interactions (PPIs) represent a large class of disease-relevant molecular targets where the binding interface is often challenging to target with a small molecule. In such cases, peptides sequences that mimic a key portion of the interacting protein interface provide an important alternative but are subject to a key limitation: once separate from the whole protein a short peptide sequence no longer retains its (bioactive) conformation. A means to tackle this issue for helical peptides is using a synthetic peptide ‘staple’ which locks the peptide sequence into a bioactive conformation.
Another commonly used class of molecules used to target protein-protein interactions are helix mimetics. Helix mimetics are a unique class of PPI inhibitor since they present binding groups in approximately the same orientation as key amino acid residues in the helical component of a PPI.
We are using these two methodologies to target PPIs involve in infectious disease by targeting key interactions in both bacteria and malaria parasites. We are also using synthetic chemistry to impart additional function onto these inhibitors to improve their biological function.
If you are interested in initiating a collaboration we would be happy to hear from you. Please contact Dr Anna Barnard.
We are grateful to the following organisations for financial support: