Cellular Internalization of Water-Soluble Helical Aromatic Amide Foldamers
Cellular Internalization of Water-Soluble Helical Aromatic Amide Foldamers
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DOI：
10.1002/cbic.201000256
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发表时间：
2010-08-16
期刊：
影响因子：
3.2
通讯作者：
Huc, Ivan
中科院分区：
文献类型：
--
作者：
Iriondo-Alberdi, Jone;Laxmi-Reddy, Katta;Huc, Ivan
药物和治疗剂的细胞内转运代表了化学、生物学和医学界面上最令人兴奋和最具挑战性的领域之一。迄今为止，该领域的大部分努力都致力于开发基于肽的递送系统，这些系统可以将治疗剂转运到细胞内靶点。最近，生物启发的非天然折叠体的使用已经导致货物分子的成功递送，其具有宽范围的大小和跨细胞膜的物理化学性质。我们在此报道了芳香酰胺折叠体的合成，它们作为细胞穿透剂的生物学评价通过使用成熟的合成路线，构建了一系列荧光素标记的阳离子芳基酰胺缀合物，并通过流式细胞术和荧光显微镜分析了它们在各种人细胞系中的细胞摄取。分析显示，较长的寡聚体实现了更大的细胞易位，八聚体Q8被证明是所有三种细胞系的显着载体。生物学研究还表明，这些螺旋是生物相容的，因此显示出它们作为细胞穿透剂和作为载体将生物活性分子递送到细胞中的应用前景。
The intracellular transport of drugs and therapeutics represents one of the most exciting and challenging areas at the interface of chemistry, biology, and medicine Most of the effort in this field so far has been devoted to the development of peptide-based delivery systems that can translocate therapeutic agents into their intracellular targets More recently, the use of bio-inspired non-natural foldamers has resulted in the successful delivery of cargo molecules, which possess a wide range of sizes and physicochemical properties across the cell membrane We report herein the synthesis of aromatic amide foldamers and their biological evaluation as cell-penetrating agents By using a well-established synthetic route, a series of fluorescein-labeled cationic aryl amide conjugates has been constructed, and their cellular uptake into various human cell lines has been analyzed by flow cytometry and fluorescence microscopy. The assays revealed that longer oligomers achieve greater cellular translocation, with octamer Q8 proving to be a remarkable vehicle for all three cell lines. Biological studies have also indicated that these helices are biocompatible, thus showing promise in their application as cell-penetrating agents and as vehicles to deliver biologically active molecules into cells.