Cone-shaped foldamers for saccharide recognition in water

碳水化合物识别介导了广泛的生物过程。因此，开发能够在生物介质中具有高结合亲和力和选择性的碳水化合物的合成受体已经成为产生特异性生物标志物的长期目标，所述特异性生物标志物可用于成像、早期诊断和连续体内监测，并且甚至可提供作为治疗剂的新机会。然而，由于碳水化合物的亲水性和微妙的结构多样性，使它们难以结合和区分，进展缓慢。即使是碳水化合物结合蛋白（凝集素）-研究和医学的重要工具-也显示出明显的低结合亲和力和适度的选择性。近年来，芳香族低聚酰胺螺旋折叠体胶囊在有机溶剂中识别碳水化合物方面表现出无与伦比的性能。具体而言，它们的明确定义和相对刚性的结合腔导致了出色的碳水化合物选择性。该项目旨在进一步阐述基于折叠体的受体，使其在水中工作。该方法依赖于：（1）将硼酸官能团引入折叠体序列中，以将硼酸的碳水化合物共价结合性质与折叠体结合空腔的形状选择性结合联合收割机;（2）开发新的受体结构，即能够靶向生物学相关底物如位于蛋白质上的糖基残基的开放末端锥形螺旋;（3）研究它们的光学行为，并可能插入光响应单元，将它们变成传感器。

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.