Genetically Encoded Sensor Cells for the Screening of Glucocorticoid Receptor (GR) Effectors in Herbal Extracts
| Autor: | Youngeun Kwon, Chungwon Kang, Soyoun Kim, Minhyeong Lee, Jeahee Ryu, Euiyeon Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Signal peptide
Clinical Biochemistry Cell Anti-Inflammatory Agents Drug Evaluation Preclinical Biosensing Techniques Computational biology cortisol signal peptide reconstitution Article conditional protein splicing (CPS) chemistry.chemical_compound Receptors Glucocorticoid Glucocorticoid receptor cell-based sensor Cell Line Tumor medicine Animals Humans drug screening Natural product Plant Extracts Effector Deer glucocorticoid receptor (GR) Biological activity General Medicine In vitro medicine.anatomical_structure chemistry TP248.13-248.65 Function (biology) Biotechnology |
| Zdroj: | Biosensors Volume 11 Issue 9 Biosensors, Vol 11, Iss 341, p 341 (2021) |
| ISSN: | 2079-6374 |
| DOI: | 10.3390/bios11090341 |
| Popis: | Although in vitro sensors provide facile low-cost ways to screen for biologically active targets, their results may not accurately represent the molecular interactions in biological systems. Cell-based sensors have emerged as promising platforms to screen targets in biologically relevant environments. However, there are few examples where cell-based sensors have been practically applied for drug screening. Here, we used engineered cortisol-detecting sensor cells to screen for natural mimetics of cortisol. The sensor cells were designed to report the presence of a target through signal peptide activation and subsequent fluorescence signal translocation. The developed sensor cells were able to detect known biological targets from human-derived analytes as well as natural product extracts, such as deer antlers and ginseng. The multi-use capability and versatility to screen in different cellular environments were also demonstrated. The sensor cells were used to identify novel GR effectors from medicinal plant extracts. Our results suggest that decursin from dongquai had the GR effector function as a selective GR agonist (SEGRA), making it a potent drug candidate with anti-inflammatory activity. We demonstrated the superiority of cell-based sensing technology over in vitro screening, proving its potential for practical drug screening applications that leads to the function-based discovery of target molecules. |
| Databáze: | OpenAIRE |
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