Metal Complexes as Inhibitors of Protein-Protein Interactions

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Although many cellular processes depend upon enzymatic reactions, protein-protein interactions populate a significant number of regulatory pathways. Thus an explosion of interest in their study mirrors a pivotal role in diseased states. In order to manipulate biological systems effectively, there is a pressing need for small molecules that inhibit these interactions through strong and selective recognition of the interacting surfaces. The internal 'lock and key' type enzyme-substrate molecular recognition model has led to a good understanding of how to design small molecule inhibitors. However, it is not clear how the external 'hand gripping a ball' type recognition that occurs in protein-protein interactions, can be replicated using small molecules. Protein-protein interactions involve complementary large shapeless surfaces with multiple non-covalent contacts. In this work we will use small, easy to make, building-blocks that can be brought together using either a template directed synthesis, or self-organisation, to make 'protein surface mimics'; molecular entities that possess the molecular information necessary to recognise a protein surface and block the interaction it makes with its partner. Template- directed synthesis and self-assembly are methods used to assemble complex architectures from smaller components. They use the information within the components as an instruction set for the construction of the complex architecture. Methods that can do this are essential to the development of new strategies to understand and combat disease.