Cone-shaped foldamers for saccharide recognition in water

用于水中糖识别的锥形折叠器

• 批准号: 505433898
• 负责人: Professor Dr. Ivan Huc
• 金额: --
• 依托单位: Fach Pharmazeutische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/505433898?language=en
• 关键词: Cone; shaped; foldamers; saccharide; recognition

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.

碳水化合物识别介导了广泛的生物过程。因此，开发在生物介质中具有高结合亲和力和选择性的碳水化合物合成受体一直是一个长期存在的目标，以生产可用于成像，早期诊断和连续体内监测的特定生物标志物，甚至可能为治疗提供新的机会。然而，由于碳水化合物的亲水性和微妙的结构多样性，使它们难以结合和相互区分，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——也表现出明显的低结合亲和力和适度的选择性。近年来，芳香低聚酰胺螺旋折叠体胶囊在识别有机溶剂中的碳水化合物方面表现出了无与伦比的性能。具体来说，它们定义明确且相对刚性的结合腔导致了出色的碳水化合物选择性。该项目打算进一步细化基于折叠体的受体，使其在水中发挥作用。该方法依赖于：(1)将硼酸官能团引入折叠体序列，将硼酸的碳水化合物共价结合特性与折叠体结合腔的形状选择性结合起来；(2)开发一种新的受体结构，即开放式锥形螺旋结构，能够靶向生物相关底物，如位于蛋白质上的糖基残基；(3)研究它们的光学行为，并可能插入光响应单元将其转变为传感器。