Synthetic anion transporters provide a promising avenue to treat diseases such as cystic fibrosis and cancer. Anion binding site preorganization is one aspect of transporter design that can be manipulated to enhance binding. Macrocycles possess preorganized binding cavities, enabling more selective and efficient anion binding and transport. In this study, we build on a macrocyclic tetralactam scaffold by preparing a series of fluorinated and non-fluorinated tetralactam anion transporters. Anion binding and transport assays were used to analyze the substituent effects on scaffold lipophilicity, selectivity, solubility, binding strength, and transport rates. The series was analyzed for the ability to bind and transport Cl⁻ and F⁻ anions across lipid bilayers. Some highly fluorinated tetralactams display extremely high levels of Cl⁻ and F⁻ transport activity, showing record activities in 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) assays and a Eu(III) probe-based F⁻ transport assay.

中文翻译：

---

基于四内酰胺的阴离子转运蛋白


合成阴离子转运蛋白为治疗囊性纤维化和癌症等疾病提供了一条有前途的途径。阴离子结合位点预组织是转运蛋白设计的一个方面，可以对其进行操作以增强结合。大环具有预组织化的结合腔，可实现更具选择性和高效的阴离子结合和转运。在这项研究中，我们通过制备一系列氟化和非氟化四内酰胺阴离子转运蛋白，在大环四内酰胺支架的基础上构建。阴离子结合和转运测定用于分析取代基对支架亲脂性、选择性、溶解度、结合强度和转运速率的影响。分析了该系列跨脂质双层结合和转运 Cl^-和 F^--阴离子的能力。一些高度氟化的四内酰胺显示出极高水平的 Cl^-和 F^--转运活性，在 8-羟基芘-1,3,6-三磺酸 （HPTS） 测定和基于 Eu（III） 探针的 F^-转运测定中显示出创纪录的活性。