BOPPY-based novel fluorescent dopamine D₂ and D₃ receptor ligands

Area of Science:

• Neuroscience
• Organic Chemistry
• Pharmacology

Background:

• Dopamine is a key neurotransmitter implicated in neurological disorders.
• Dopamine D2 and D3 receptors are significant targets for therapeutic intervention.
• BODIPY dyes are useful for fluorescence labeling but structurally distinct pyridine-based moieties are explored.

Purpose of the Study:

• To develop novel fluorescent ligands for dopamine D2 and D3 receptors.
• To explore the utility of BOPPY fluorophores in labeling GPCR ligands.
• To create bright fluorescent ligands with high binding affinity.

Main Methods:

• Synthesis of BOPPY-labeled ligands targeting D2R/D3R pharmacophores.
• Evaluation of binding affinities of the synthesized ligands.
• Assessment of quantum yields for fluorescence properties.

Main Results:

• Novel BOPPY-labeled ligands for dopamine D2 and D3 receptors were successfully synthesized.
• Ligands exhibited moderate to low nanomolar binding affinities.
• Achieved low to excellent quantum yields, resulting in bright fluorescent ligands.

Conclusions:

• This study reports the first application of BOPPY fluorophores to GPCR ligands.
• The BOPPY labeling approach is versatile for fluorescence labeling via primary aliphatic amines.
• This strategy provides a general method for developing fluorescent probes for neuroscience research.