2. Academic Validation
  3. TEPP-46-Based AIE Fluorescent Probe for Detection and Bioimaging of PKM2 in Living Cells

TEPP-46-Based AIE Fluorescent Probe for Detection and Bioimaging of PKM2 in Living Cells

  • Anal Chem. 2021 Sep 21;93(37):12682-12689. doi: 10.1021/acs.analchem.1c02529.
Dong Wang 1,  Chunmeng Li 2,  Ya Zhu 2,  Yunxia Song 2,  Sheng Lu 3,  Huiyong Sun 4,  Haiping Hao 1,  Xiaowei Xu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 210009 Nanjing, China.
  • 2 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 210009 Nanjing, China.
  • 3 State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, 211816 Nanjing, China.
  • 4 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, 210009 Nanjing, China.
PMID: 34505513 DOI: 10.1021/acs.analchem.1c02529
Abstract

Pyruvate Kinase (PK) M2 (PKM2), a glycolytic Enzyme, is a hallmark of different types of tumors and plays a significant role in the Warburg effect. However, there is no fluorescent probe for PKM2 that has been reported yet. In this study, TEPC466, a novel TEPP-46-based aggregation-induced emission (AIE) probe for the detection of PKM2, was designed, synthesized, and fully characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry. When the fluorescent agent, coumarine, was conjugated to TEPP-46, the bioprobe TEPC466 showed a high degree of selectivity and sensitivity for the detection of PKM2 protein via the AIE effect. TEPC466 was then successfully applied in imaging the PKM2 protein in colorectal Cancer cells with low toxicity. Moreover, structure-based modeling and the PK activity assay confirmed that TEPC466 has a better binding with PKM2 than TEPP-46, which suggests that TEPC466 could also be a good agonist of PKM2. Taken together, the bioprobe shows potential in selective detection of PKM2 and provides a useful tool for Cancer diagnosis and therapy.

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