Ligand–receptor interaction platforms and their applications for drug discovery

Abstract

Introduction: The study of drug–target interactions is essential for the understanding of biological processes and for the efforts to develop new therapeutic molecules. Increased ligand-binding assays have coincided with the advances in reagents, detection and instrumentation technologies, the expansion in therapeutic targets of interest, and the increasingly recognized importance of biochemical aspects of drug–target interactions in determining the clinical performance of drug molecules. Nowadays, ligand-binding assays can determine every aspect of many drug–target interactions.

Areas covered: Given that ligand–target interactions are very diverse, the author has decided to focus on the binding of small molecules to protein targets. This article first reviews the key biochemical aspects of drug–target interactions, and then discusses the detection principles of various ligand-binding techniques in the context of their primary applications for drug discovery and development.

Expert opinion: Equilibrium-binding affinity should not be used as a solo indicator for the in vivo pharmacology of drugs. The clinical relevance of drug-binding kinetics demands high throughput kinetics early in drug discovery. The dependence of ligand binding and function on the conformation of targets necessitates solution-based and whole cell-based ligand-binding assays. The increasing need to examine ligand binding at the proteome level, driven by the clinical importance of the polypharmacology of ligands, has started to make the structure-based in silico binding screen an indispensable technique for drug discovery and development. Integration of different ligand-binding assays is important to improve the efficiency of the drug discovery and development process.

Keywords::

• affinity
• backscattering interferometry
• biochemical mechanism of action
• biolayer interferometry
• calorimetry
• conformation
• crystallography
• drug–target interaction
• fluorescence
• in silico screening
• kinetics
• label-free
• ligand-binding techniques
• microfluidics
• nuclear magnetic resonance
• plasmon-waveguide resonance
• polypharmacology
• protein thermal denaturation
• radioligand binding
• rebinding
• residence time
• resonant waveguide grating
• surface acoustic wave
• surface plasmon resonance
• thermodynamics
• whispering gallery mode

Notes

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