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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
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Profiling novel pharmacology of receptor complexes using Receptor-HIT
Elizabeth K M Johnstone1,2,3, Kevin D G Pfleger1,2,3,4
1Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia 6009, Australia.
Biochemical Society Transactions
|August 26, 2021
Summary
Receptor heteromers offer novel drug targets with enhanced specificity. Receptor-HIT technology detects these complexes in real-time using proximity-based bioluminescence resonance energy transfer (BRET) for pharmacological quantification.
Area of Science:
- Biochemistry and Pharmacology
- Molecular Biology
- Drug Discovery
Background:
- Receptor heteromerisation forms complexes with unique pharmacological profiles.
- These heteromers represent promising, highly specific drug targets.
- Targeting heteromers offers potential for increased selectivity over individual receptors.
Purpose of the Study:
- Introduce Receptor-Heteromer Investigation Technology (Receptor-HIT).
- Demonstrate Receptor-HIT's capability for real-time detection of receptor heteromers.
- Highlight the functional and pharmacological quantification of heteromer activity.
Main Methods:
- Utilize proximity-based reporter systems, specifically bioluminescence resonance energy transfer (BRET).
- Employ ligand-induced signals from altered biomolecular interactions (ligands, proteins) for detection.
- Monitor receptor interactions in live cells for real-time analysis.
Main Results:
- Receptor-HIT successfully detects receptor heteromers in live cells.
- The technology enables real-time monitoring of heteromer formation and function.
- Functional information regarding heteromer activity can be pharmacologically quantified.
Conclusions:
- Receptor-HIT is a versatile technology for studying receptor heteromers.
- Applications span various receptor classes, including GPCRs and RTKs.
- The technology supports intracellular, extracellular, and genome-edited endogenous protein studies.
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