Synthetic organic approaches for covalent inhibition of protein-protein interactions

The project will involve the application of a full range of synthetic organic chemistry methods to design and construct conformationally well-defined molecules (foldamers) that covalently recognise key elements of protein surfaces. These scaffolds will form a toolkit of chemical probes for proteins that lie at the heart of intractable disease. Specific objectives of the project are: (i) the design, synthesis, and characterisation of new peptidomimetic scaffolds bearing covalent warheads; (ii) investigation of their ability to mediate the behaviour of therapeutically-relevant proteins; (iii) 'catch and modify' - chemical post-translational modification of amino acid side-chains.