Fluorescent tools for imaging class A G-protein coupled receptors

Area of Science:

• Biochemistry and Pharmacology
• Molecular Biology
• Drug Discovery

Background:

• G protein-coupled receptors (GPCRs) are crucial in biological processes and are major drug targets.
• Many GPCRs, especially orphan receptors, require further investigation.
• Fluorescent ligands are vital tools for characterizing GPCRs' function and organization.

Purpose of the Study:

• To review recent advances in fluorescent probe development for Class A GPCRs (2018-2024).
• To analyze the distribution of new probes across GPCR subclasses and identify newly targeted receptors.
• To highlight the impact of structural biology advancements on fluorescent probe design.

Main Methods:

• Systematic review of fluorescent probe development for Class A GPCRs published between 2018 and 2024.
• Analysis of over 120 newly developed probes targeting 60 GPCRs.
• Integration of data with recent structural biology findings (cryo-EM, AlphaFold).

Main Results:

• Development of novel fluorescent probes for 12 new receptor subtypes and 6 orphan GPCRs (e.g., GPR6, GPR52, GPR84).
• Significant progress in probe selectivity across diverse GPCR families (aminergic, peptidergic, lipid, etc.).
• Enhanced understanding of GPCRs due to structural biology advancements facilitating probe design.

Conclusions:

• Fluorescent probes are increasingly vital for GPCR research and drug discovery.
• Recent innovations enable broader GPCR targeting, including previously uncharacterized receptors.
• These tools support advanced applications like in vivo imaging, diagnostics, and fluorescence-guided surgery, accelerating drug development.