Native mass spectrometry (MS) is a powerful technique for interrogating membrane protein complexes and their interactions with other molecules. A key aspect of the technique is the ability to preserve native-like structures and noncovalent interactions, which can be challenging depending on the choice of detergent. Different strategies have been employed to reduce charge on protein complexes to minimize activation and preserve non-covalent interactions. Here, we report the synthesis of a class of polyamine detergents tailored for native MS studies of membrane proteins. These detergents, a series of spermine covalently attached to various alkyl tails, are exceptional charge-reducing molecules, exhibiting a ten-fold enhanced potency over spermine. Addition of polyamine detergents to proteins solubilized in maltoside detergents results in improved, charge-reduced native mass spectra and reduced dissociation of subunits. Polyamine detergents open new opportunities to investigate membrane proteins in different detergent environments that have thwarted previous native MS studies.

天然质谱 (MS) 是一种用于研究膜蛋白复合物及其与其他分子相互作用的强大技术。该技术的一个关键方面是能够保留类天然结构和非共价相互作用，这可能具有挑战性，具体取决于洗涤剂的选择。人们采用了不同的策略来减少蛋白质复合物上的电荷，以最大限度地减少激活并保留非共价相互作用。在这里，我们报告了一类专为膜蛋白的天然 MS 研究而定制的多胺去污剂的合成。这些去污剂是一系列共价连接到各种烷基尾部的精胺，是特殊的电荷减少分子，其效力比精胺增强十倍。将聚胺去污剂添加到溶解在麦芽糖苷去污剂中的蛋白质中，可以改善、电荷减少的天然质谱并减少亚基的解离。多胺去污剂为研究不同去污剂环境中的膜蛋白提供了新的机会，而这些环境阻碍了之前的天然 MS 研究。