The chronological evolution of fluorescent GPCR probes for bioimaging

Scientists Robert J. Lefkowitz and Brian K. Kobilka won the Nobel Prize in 2012 for reporting a groundbreaking discovery that revealed a crucial member of the receptor family, the G-protein-coupled receptors (GPCRs). GPCRs are the collective names for over 1,000 seven-transmembrane receptors that are responsible for multiple types of cell signaling responses. When activated by various stimuli (e.g., photons and small molecules), GPCRs interact with intracellular proteins to mediate downstream signals. The role of GPCRs in physiological and pathological processes renders them candidate targets in the development of many drugs. Recent research on GPCR structural biology has considerably improved our knowledge of GPCR signaling. However, the precise binding mechanism of diverse ligands to GPCRs to generate unique signal transduction and the involvement of GPCRs in disease pathogenesis remain controversial. The designing of tools for studying the pharmacology of GPCRs is critical to identifying safer and more effective therapies. Various molecular probes for investigating receptor structure and function have proven essential in GPCR research. This review summarizes the physiological functions of some GPCRs and discusses the molecular design strategies, applications, and development status of small molecule organic fluorescence probes of various GPCRs in humans.