Cone-shaped foldamers for saccharide recognition in water

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Carbohydrate recognition mediates a wide range of biological processes. Developing synthetic receptors for carbohydrates capable of both high binding affinity and selectivity in biological media has thus been a long standing objective to produce specific biomarkers that could be useful for imaging, early stage diagnostic, and continuous in vivo monitoring, and that may even offer new opportunities as therapeutics. However, progress has been slow due to carbohydrates’ hydrophilic nature and subtle structural diversity that make them hard to bind and to discriminate from one another. Even carbohydrate binding proteins (lectins) – an important tool for research and medicine - show notably low binding affinity and modest selectivity. In recent years, aromatic oligoamide helical foldamer capsules have demonstrated unmatched performances at recognizing carbohydrates in organic solvents. Specifically, their well-defined and relatively rigid binding cavities resulted in outstanding carbohydrate selectivity. This project intends to further elaborate foldamer-based receptors to make them work in water. The approach relies on: (1) Incorporating boronic acid functionalities into foldamer sequences to combine the carbohydrate covalent binding properties of the boronic acids with the shape selectivity of foldamer binding cavities; (2) Developing a novel receptor architecture, namely an open-ended cone-shape helix able to target biologically relevant substrates such as glycosyl residues located on proteins; and (3) Studying their optical behavior and possibly inserting photo-responsive units to turn them into sensors.