With the aggravated burden of opioid use disorder spreading worldwide, demands for new forms of opioid receptor agonist/antagonist constitute immense research interest. The Mu-opioid receptor (MOR) is currently in the spotlight on account of its general involvement in opioid-induced antinociception, tolerance and dependence. MOR binding assay, however, is often complicated by difficulty in MOR separation and purification, as well as the tedious procedure in standard biolayer interferometry and surface plasmon resonance measurements. To this end, we present TPE2N as a light-up fluorescent probe for MOR, which exhibits satisfactory performance in both live cells and lysates. TPE2N was elaborately designed based on the synergistic effect of twisted intramolecular charge-transfer and aggregation-induced emission by incorporating a tetraphenylethene unit to emit strong fluorescence in a restrained environment upon binding with MOR through the naloxone pharmacore. The developed assay enabled high-throughput screening of a compound library, and successfully identified three ligands as lead compounds for further development.

随着阿片类药物使用障碍在全球蔓延的加重负担，对新型阿片类受体激动剂/拮抗剂的需求构成了巨大的研究兴趣。Mu-阿片受体 (MOR) 目前备受关注，因为它普遍参与阿片类药物诱导的镇痛作用、耐受性和依赖性。然而，MOR 结合测定通常因 MOR 分离和纯化困难以及标准生物层干涉测量和表面等离子体共振测量中的繁琐程序而变得复杂。为此，我们提出 TPE2N 作为发光荧光探针对于 MOR，它在活细胞和裂解物中均表现出令人满意的性能。TPE2N 是基于扭曲分子内电荷转移和聚集诱导发光的协同效应精心设计的，通过结合四苯乙烯单元在通过纳洛酮药核与 MOR 结合后在受限环境中发出强荧光。开发的检测方法能够对化合物库进行高通量筛选，并成功地将三种配体鉴定为先导化合物以供进一步开发。