南开大学郭东升团队扩展偶氮基杯[4]芳烃的疏水腔面以实现生物素/亲和素的控释。相关论文于2024年4月2日发表在《德国应用化学》杂志上。

开发将超高亲和力和对活性客体的可控释放相结合的人工受体，在生物医学应用中具有重要意义。一方面，具有极高结合亲和力的复合物可以抵抗生理环境中稀释效应，和复杂干扰物诱导的不希望的解离。另一方面，客体的刺激反应性释放对于准确激活其功能至关重要。

在这种情况下，研究人员扩展了缺氧反应性偶氮杯[4]芳烃的疏水腔表面，提供了Naph-SAC4A。这种修饰显著增强了其对1013 M1的水性结合亲和力，类似于天然存在的最强识别对生物素/（strept-）抗生物素。因此，Naph-SAC4A成为第一个同时整合超高识别亲和力和主动可控释放的人工受体。

显著增强的亲和力不仅提高了Naph-SAC4A在检测血清中罗库溴化铵时的灵敏度，而且在细胞水平上提高了缺氧反应性阿霉素递送的准确性，证明了其在各种实际应用中的巨大潜力。

附：英文原文

Title: Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release

Author: Fang-Yuan Chen, Cheng-Zhi Li, Han Han, Wen-Chao Geng, Shu-Xin Zhang, Ze-Tao Jiang, Qing-Yu Zhao, Kang Cai, Dong-Sheng Guo

Issue&Volume: 2024-04-02

Abstract: The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

DOI: 10.1002/anie.202402139

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202402139