Chen Fang-Yuan, Fu Rong, Gong Zhihao, Li Chunju, Guo Dong-Sheng, Cai Kang
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), Frontiers Science Center for New Organic Matter, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin, 300071, China.
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin, 300071, China.
Angew Chem Int Ed Engl. 2025 Jul;64(29):e202500916. doi: 10.1002/anie.202500916. Epub 2025 Apr 27.
Aqueous-phase molecular recognition pairs with ultrahigh binding affinity hold immense value in biotechnology and chemical applications. However, the rational design of synthetic pairs with such exceptional binding strength has long remained a significant challenge, with notable progress achieved only in recent years. In this minireview, we begin by defining the term "ultrahigh-affinity" through a comprehensive analysis of available data on aqueous-phase molecular recognition by water-soluble macrocyclic hosts. Based on this foundation, we provide a detailed overview of the latest advancements in various classes of ultrahigh-affinity receptors, extracting key design principles that drive their remarkable performance. We further highlight emerging applications of ultrahigh-affinity molecular pairs in biomedical materials, spanning bioorthogonal chemistry, biosensing, bioimaging, drug delivery, and toxin sequestration. These examples underscore the transformative potential of ultrahigh-affinity recognition in addressing real-world biomedical challenges. Finally, we offer a forward-looking perspective on the future of this rapidly evolving field, exploring potential directions for designing more diverse and functional ultrahigh-affinity molecular recognition tools. By bridging the gap between fundamental science and practical applications, this minireview aims to inspire the development of next-generation molecular recognition systems and foster deeper integration between supramolecular chemistry and biomedical materials, paving the way for innovative solutions to pressing biomedical needs.
具有超高结合亲和力的水相分子识别对在生物技术和化学应用中具有巨大价值。然而，合理设计具有如此卓越结合强度的合成对长期以来一直是一项重大挑战，直到近年来才取得显著进展。在本综述中，我们首先通过全面分析水溶性大环主体对水相分子识别的现有数据来定义“超高亲和力”这一术语。在此基础上，我们详细概述了各类超高亲和力受体的最新进展，提炼出驱动其卓越性能的关键设计原则。我们进一步强调了超高亲和力分子对在生物医学材料中的新兴应用，涵盖生物正交化学、生物传感、生物成像、药物递送和毒素螯合。这些例子凸显了超高亲和力识别在应对现实世界生物医学挑战方面的变革潜力。最后，我们对这个快速发展的领域的未来提供了前瞻性展望，探索设计更多样化和功能性超高亲和力分子识别工具的潜在方向。通过弥合基础科学与实际应用之间的差距，本综述旨在激发下一代分子识别系统的发展，并促进超分子化学与生物医学材料之间的更深入整合为紧迫的生物医学需求提供创新解决方案铺平道路。
