Bioluminescent Probe for Monitoring Endogenous Fibroblast Activation Protein-Alpha

  • Anal Chem. 2019 Dec 3;91(23):14873-14878. doi: 10.1021/acs.analchem.9b02117.
Yuxing Lin  1  2 ,  Zhao Ma  1 ,  Zhenzhen Li  1 ,  Yuqi Gao  1 ,  Xiaojun Qin  1 ,  Zheng Zhang  1 ,  Guankai Wang  1 ,  Lupei Du  1 ,  Minyong Li  1  3
Affiliations
  • 1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy , Shandong University , Jinan , Shandong 250012 , China.
  • 2. Institute of Medical Sciences , Second Hospital of Shandong University , Jinan , Shandong 250033 , China.
  • 3. State Key Laboratory of Microbial Technology , Shandong University , Jinan , Shandong 250100 , China.
PMID: 31670506 DOI: 10.1021/acs.analchem.9b02117
Abstract

Fibroblast activation protein-α (FAP), as a crucial member of cell surface glycoprotein, highly expresses in reactive fibroblasts of tumors and several fibrosis diseases. It is a potential target for drug design and also reported as a prodrug strategy to increase the therapeutic window of some Anticancer agents. In this work, we developed the first bioluminogenic probe for FAP with a limit-of-detection of 0.254 ng/mL, which could be applied to evaluate the FAP inhibitors in vitro. The experiments of transgenic mice and tumor-bearing nude mice validated our probe 1 could reflect the endogenous FAP level in vivo. Furthermore, this probe was successfully used to reflect FAP up-regulation in the lung homogenates of the bleomycin-induced idiopathic pulmonary fibrosis mice.

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