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

  • Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 15:327:125394. doi: 10.1016/j.saa.2024.125394.
Xiangwei Ma  1 ,  Zhenzhong Yang  2 ,  Yuanlin Luo  3 ,  Zehua Jin  4 ,  Jingtao Zou  5 ,  Yi Wang  6 ,  Xiaoping Zhao  7
Affiliations
  • 1. School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou 310053, China.
  • 2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Chinese Medicine Modernization, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 3. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 4. State Key Laboratory of Chinese Medicine Modernization, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 5. Tonghua Huaxia Pharmaceutical Company, Tonghua 134000, China.
  • 6. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Chinese Medicine Modernization, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: [email protected].
  • 7. School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: [email protected].
PMID: 39520822 DOI: 10.1016/j.saa.2024.125394
Abstract

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.

Keywords
Aggregation-induced emission; Fluorescent probe; Natural product library; Protein tyrosine phosphatase 1B.
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