SUPRACHEMBIO · Supramolecular Chemical Biology Modulation of Protein-Protein Interactions

This proposal aims to explore the combination of supramolecular chemistry with chemical biology. Supramolecular architectures are proposed for the modulation of protein-protein interactions. Two general themes are outlined; 1) supramolecular chemistry in the cell and 2) supramolecular multivalency. Supramolecular architectures are brought forward as excellent tools to control protein-protein interactions at the cellular level. Supramolecular elements, selectively attached to proteins, are outlined to control protein dimerization and localization. The introduction of different supramolecular elements, either in vitro or in vivo via specific labeling techniques, is part of the plan, including the introduction of supramolecular elements, whose interactions can be reversibly switched with light. With these systems, the temporal control over protein-protein interactions and protein localization can be addressed. Self-assembling multivalent architectures are proposed as optimal scaffolds and flexible systems for recognition and binding of cells. The assembly process of the supramolecular architecture will be steered via interplay with the characteristics of the cellular target and the environment, controlling size, shape and composition. This self-assembling multivalent platform will be applied to control or initiate interactions between different types of surfaces, such as cells, antigens and chips. The self-assembling scaffolds additionally provide an ideal platform to be combined with proteins, allowing the generation of ordered protein wires, with control over orientation and distances between proteins. The combination of supramolecular chemistry with chemical biology is envisioned to enable the modulation of protein-protein interactions and thus provide entries to this long standing fundamental challenge.