Synthetic Strategies for Dynamic Covalent Protein Recognition

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The project will focus on the design and synthesis of conformationally pre-organised molecules (peptidomimetic foldamers) that recognise key elements of protein surfaces. These scaffolds will form a toolkit of chemical probes to target: (i) protein-protein interactions (PPIs) and; (ii) proteins prone to misfolding. Aberrant control of these systems lies at the heart of many diseases such as cancer, diabetes and neurodegeneration (Alzheimer's, Parkinson's, and others).The Specific objectives of the project are the: (i) design, synthesis, and characterisation of new peptidomimetic foldamers; (ii) attachment of covalent warheads that can form bonds selectively with amino side-chains on the target protein; (iii) investigation of their ability to mediate the behaviour of therapeutically-relevant proteins.