Membrane protein structures provide a fundamental understanding of their molecular actions and are of importance for drug development. Detergents are widely used to solubilize, stabilize, and crystallize membrane proteins, but membrane proteins solubilized in conventional detergents are prone to denaturation and aggregation. Thus, developing novel detergents with enhanced efficacy for protein stabilization remains important. We report herein the design and synthesis of a class of phenol-derived maltoside detergents. Using two different linkers, we prepared two sets of new detergents, designated maltose-bis(hydroxymethyl)phenol (MBPs) and maltose-tris(hydroxymethyl)phenol (MTPs). The evaluation of these detergents with three transporters and two G-protein coupled receptors allowed us to identify a couple of new detergents (MBP-C9 and MTP-C12) that consistently conferred enhanced stability to all tested proteins compared to a gold standard detergent (DDM). Furthermore, the data analysis based on the detergent structures provides key detergent features responsible for membrane protein stabilization that together will facilitate the future design of novel detergents.

中文翻译：

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麦芽糖-双（羟甲基）苯酚（MBP）和麦芽糖-三（羟甲基）苯酚（MTP）两亲物用于膜蛋白稳定性

膜蛋白结构提供了对其分子作用的基本理解，对药物开发具有重要意义。去污剂广泛用于溶解、稳定和结晶膜蛋白，但溶解在常规去污剂中的膜蛋白容易变性和聚集。因此，开发具有增强蛋白质稳定功效的新型洗涤剂仍然很重要。我们在此报告了一类苯酚衍生的麦芽糖苷去垢剂的设计和合成。使用两种不同的接头，我们制备了两组新的去污剂，分别命名为麦芽糖-双（羟甲基）苯酚（MBP）和麦芽糖-三（羟甲基）苯酚（MTP）。用三种转运蛋白和两种 G 蛋白偶联受体对这些去污剂的评估使我们能够鉴定出几种新去污剂（MBP-C9 和 MTP-C12），与金标准去污剂（DDM）相比，这些去污剂始终赋予所有测试蛋白质更高的稳定性）。此外，基于去污剂结构的数据分析提供了负责膜蛋白稳定的关键去污剂特征，这将共同促进新型去污剂的未来设计。