Toward fluorescent probes for G-protein-coupled receptors (GPCRs).

G-protein-coupled receptors (GPCRs), a superfamily of cell-surface receptors that are the targets of about 40% of prescription drugs on the market, can sense numerous critical extracellular signals. Recent breakthroughs in structural biology, especially in holo-form X-ray crystal structures, have contributed to our understanding of GPCR signaling. However, actions of GPCRs at the cellular and molecular level, interactions between GPCRs, and the role of protein dynamics in receptor activities still remain controversial. To overcome these dilemmas, fluorescent probes of GPCRs have been employed, which have advantages of in vivo safety and real-time monitoring. Various probes that depend on specific mechanisms and/or technologies have been used to study GPCRs. The present review focuses on surveying the design and applications of fluorescent probes for GPCRs that are derived from small molecules or using protein-labeling techniques, as well as discussing some design strategies for new probes.