This Account summarizes the progress in protein–calixarene complexation, tracing the developments from binary recognition to the glue activity of calixarenes and beyond to macrocycle-mediated frameworks. During the past 10 years, we have been tackling the question of protein–calixarene complexation in several ways, mainly by cocrystallization and X-ray structure determination as well as by solution state methods, NMR spectroscopy, isothermal titration calorimetry (ITC), and light scattering. Much of this work benefitted from collaboration, highlighted here. Our first breakthrough was the cocrystallization of cationic cytochrome c with sulfonato-calix[4]arene leading to a crystal structure defining three binding sites. Together with NMR studies, a dynamic complexation was deduced in which the calixarene explores the protein surface. Other cationic proteins were similarly amenable to cocrystallization with sulfonato-calix[4]arene, confirming calixarene–arginine/lysine encapsulation and consequent protein assembly. Calixarenes bearing anionic substituents such as sulfonate or phosphonate, but not carboxylate, have proven useful.

中文翻译：

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蛋白质-杯芳烃络合：从识别到组装

本报告总结了蛋白质-杯芳烃络合的进展，追踪了从二元识别到杯芳烃的胶水活性，再到大环介导的框架的发展。在过去的 10 年里，我们一直在通过多种方式解决蛋白质-杯芳烃络合的问题，主要是通过共结晶和 X 射线结构测定以及溶液状态法、NMR 光谱、等温滴定量热法 (ITC) 和光散射。这项工作的大部分受益于协作，此处着重说明。我们的第一个突破是阳离子细胞色素c的共结晶磺酸基杯[4]芳烃导致定义三个结合位点的晶体结构。与 NMR 研究一起，推断出杯芳烃探索蛋白质表面的动态络合。其他阳离子蛋白同样适用于与磺酸基-杯[4]芳烃共结晶，证实了杯芳烃-精氨酸/赖氨酸包封和随后的蛋白质组装。带有阴离子取代基如磺酸盐或膦酸盐但不带有羧酸盐的杯芳烃已被证明是有用的。