ABSTRACT In this article, we describe the design, synthesis and transmembrane ion transport properties of a small library of molecular membrane-spanning ionophores based on dimer-forming cyclic peptide scaffolds decorated with flexible pendants. Thanks to the modular synthetic approach, it is possible to obtain a variety of α,γ-cyclic peptides with different internal diameters as well as a number of pendant groups that are perpendicularly projected from the peptide backbone. These groups are incorporated by a copper-catalysed cycloaddition between azide-modified oligo-ethylene glycol-based tentacles of different lengths and properties and cyclic peptides bearing a different number of propargyl groups attached at the amide skeleton. This methodology allowed the preparation of different ‘spanners’ and the identification of new artificial transporters that can rectify transmembranal pH gradients with EC50 values in the medium μM range. GRAPHICAL ABSTRACT

中文翻译：

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基于二聚 α,γ-环肽核心的膜扳手

摘要在本文中，我们描述了一个小型跨膜分子离子载体库的设计、合成和跨膜离子传输特性，该库基于用柔性吊坠装饰的形成二聚体的环状肽支架。由于采用模块化合成方法，可以获得各种不同内径的α，γ-环肽以及从肽主链垂直投影的许多侧基。这些基团通过铜催化的环加成在不同长度和性质的叠氮化物修饰的基于寡聚乙二醇的触角与带有不同数量的连接在酰胺骨架上的炔丙基的环肽之间掺入。这种方法允许制备不同的“扳手”并鉴定新的人工转运蛋白，这些转运蛋白可以纠正具有中等 μM 范围内的 EC50 值的跨膜 pH 梯度。图形概要