G Protein-Coupled Receptors: Immobilization and Applications in Drug Discovery

G protein-coupled receptors (GPCRs) are central in mediating many physiological
responses and widely accepted as the largest family of drug targets. Many techniques
relying on the immobilized GPCRs have been developed for high-throughput drug-
receptor interaction analysis and lead screening. However, these works have been
limited by difficulties in GPCR immobilization with high activity, high stability,
and conformational selectivity. Herein, we provide an overview of the structures,
functions, and purification of GPCR and the progress in the oriented immobilization
strategy, including affinity-based non-covalent immobilization, site-specific covalent
immobilization through bioorthogonal chemistry, and biologically mediated site-
specific immobilization. We also introduce the key biochemical aspects of drug-target
interactions and discuss the immobilized GPCRs in the drug-receptor interaction
analysis. Finally, we review the immobilized GPCRs in lead compound screening
from compound libraries and natural product extracts.