A novel fluorescent probe with Aggregation-Induced emission characteristics for PTP1B activity sensing and inhibitor screening

被引:0
|
作者
Ma, Xiangwei [1 ]
Yang, Zhenzhong [2 ,3 ]
Luo, Yuanlin [2 ]
Jin, Zehua [3 ]
Zou, Jingtao [4 ]
Wang, Yi [2 ,3 ]
Zhao, Xiaoping [5 ]
机构
[1] Zhejiang Chinese Med Univ, Sch Pharm, Hangzhou 310053, Peoples R China
[2] Zhejiang Univ, Inst Pharmaceut, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China
[3] Zhejiang Univ, Coll Pharmaceut Sci, State Key Lab Chinese Med Modernizat, Hangzhou 310058, Peoples R China
[4] Tonghua Huaxia Pharmaceut Co, Tonghua 134000, Peoples R China
[5] Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou 310053, Peoples R China
基金
中国国家自然科学基金;
关键词
Protein tyrosine phosphatase 1B; Aggregation-induced emission; Fluorescent probe; Natural product library; TYROSINE-PHOSPHATASE; 1B; LIGHT-UP PROBE; ASSAY; DISCOVERY;
D O I
10.1016/j.saa.2024.125394
中图分类号
O433 [光谱学];
学科分类号
0703 ; 070302 ;
摘要
Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for the treatment of metabolic diseases such as type 2 diabetes and obesity. In this study, a novel fluorescent probe with aggregation-induced emission (AIE) characteristics was designed and synthesized. Within the fluorescent probe, a tetraphenylethene core is connected to a peptide sequence that can be specifically recognized and hydrolysed by PTP1B. Due to the dephosphorylation of PTP1B, the fluorescent probe exhibited AIE in a turn-on manner, indicating PTP1B activity. This probe was successfully used to detect PTP1B activity in HepG2 cell lysates. Then, a probe-based method was applied to screen for potential PTP1B inhibitors from a natural product library, and three novel PTP1B inhibitors were discovered. These findings indicated that the proposed approach offered a new avenue for discovering potential PTP1B inhibitors.
引用
收藏
页数:9
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