Assembly-enhanced recognition: A biomimetic pathway to achieve ultrahigh affinities

• 成果类型: Article
• 署名作者: Chen, Fang-Yuan; Geng, Wen-Chao; Chen, Meng-Meng; Fu, Rong; Han, Han; Zhang, Zhan-Zhan; Li, Wen-Bo; Cheng, Yuan-Qiu; Li, Juan-Juan; Stoddart, J. Fraser; Cai, Kang; Guo, Dong-Sheng
• 署名单位: Collaborative Innovation Center of Chemical Science & Engineering Tianjin; Nankai University; Nankai University; University of Hong Kong; Tianjin Medical University; Northwestern University; Northwestern University; Zhejiang University; Zhejiang University; University of New South Wales Sydney
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12012
• DOI: 10.1073/pnas.2414253122
• 发表日期: 2025-01-15
• 关键词: host-guest; picomolar affinity; biotin binding; streptavidin; pair; DESIGN; ligand; water

摘要

On the one hand, nature utilizes hierarchical assemblies to create complex biological binding pockets, enabling ultrastrong recognition toward substrates in aqueous solutions. On the other hand, chemists have been fervently pursuing high-affinity recognition by constructing covalently well-preorganized stereoelectronic cavities. The potential of noncovalent assembly, however, for enhancing molecular recognition has long been underestimated. Inspired by (strept)avidin, an amphiphilic azocalix[4]arene derivative capable of assembly in aqueous solutions has been explored by us and demonstrated to exhibit ultrahigh binding affinity (up to 10(12) M-1), which is almost four orders of magnitude higher than those reported for nonassembled azocalix[4]arenes. An ultrastable azocalix[4]arene/photosensitizer complex has been applied in hypoxia-targeted photodynamic therapy for tumors. These findings highlight the immense potential of an assembly-enhanced recognition strategy in the development of the next generation of artificial receptors with appropriate functionalities and extraordinary recognition properties.