Modifications of peptides and proteins, primarily those found in chromatin, using metals such as palladium.

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The aim of the project is to use palladium-mediated cysteine bioconjugation to generate peptides and recombinant proteins bearing acetyllysine mimics. To achieve this, stable metal complexes will be employed to selectively functionalise cysteine residues to generate new side-chain functionality based on S-CAr bond formation. Subsequently, modifications that can create docking sites for bromodomains will be explored. Bromodomains are small interaction modules found on diverse proteins whereby they recognise acetyllysine residues. They are important in signalling processes involved in several therapeutic areas, most commonly in therapeutic oncology. Interactions between purified bromodomains and our new acetyllysine mimics will be evaluated using biochemical and biophysical methods. If successful, this project will provide important (bio-)chemical tools to progress the development of bromodomain inhibitors with potential application in drug discovery.