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Surface plasmon resonance biosensor combined with lentiviral particle stabilization strategy for rapid and specific screening of P-Glycoprotein ligands

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Abstract

A novel surface plasmon resonance–based P-gp ligand screening system (SPR-PLSS) combined with lentiviral particle (LVP) stabilization strategy was constructed to screen out potential P-gp inhibitors from natural products. Firstly, we constructed LVPs with high and low expression levels of P-gp. The LVPs can ensure the natural conformation of P-gp based on the principle that LVPs germinated from packaging cells will contain cell membrane fragments and P-gp they carry. Then the LVPs with high P-gp expression for active channel and LVPs with low P-gp expression for reference channel were immobilized on CM5 chip respectively. The affinity detection was thus carried out with the signal reduction on the two channels. The P-gp inhibitors, Valspodar (Val) and cyclosporin (CsA), as positive compounds, were detected to characterize the chip’s activity, and the KD of Val and CsA were 14.09 μM and 16.41 μM, respectively. Forty compounds from natural product library were screened using the SPR CM5 chip, and magnolol (Mag), honokiol (Hon), and resveratrol (Res) were screened out as potential P-gp ligands, showing a significant response signal. This work presented a novel P-gp ligand screening system based on LVP-immobilized biosensor to rapidly screen out P-gp ligands from natural product library. Compared with traditional cell experiments which the screening time may take up to several days, our method only takes several hours. Furthermore, this study has also provided solid evidences to support that some complicated membrane proteins would apply to the lentivirus-based SPR screening system.

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Funding

This research was supported by the National Natural Science Foundation of China (No.81673386, 81872829).

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  1. Yuhong Cao and Yan Cao contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai, 200433, China

    Yuhong Cao, Yan Cao, Yiwei Shi, Langdong Chen, Dongyao Wang, Yue Liu, Xiaofei Chen, Zhenyu Zhu, Zhanying Hong & Yifeng Chai

  2. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China

    Ying Cai

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  1. Yuhong Cao
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Cao, Y., Cao, Y., Shi, Y. et al. Surface plasmon resonance biosensor combined with lentiviral particle stabilization strategy for rapid and specific screening of P-Glycoprotein ligands. Anal Bioanal Chem 413, 2021–2031 (2021). https://doi.org/10.1007/s00216-021-03170-5

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  • DOI: https://doi.org/10.1007/s00216-021-03170-5

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