Small Molecule Fluorescent Ligands for the Atypical Chemokine Receptor 3 (ACKR3)

Area of Science:

• Chemical Biology
• Oncology
• Molecular Imaging

Background:

• The atypical chemokine receptor 3 (ACKR3) is implicated in cancer progression and metastasis across various cell types.
• There is a critical need for advanced chemical tools to investigate the role of ACKR3 in oncogenesis and disease pathology.

Purpose of the Study:

• To synthesize and characterize novel fluorescent probes for studying the atypical chemokine receptor 3 (ACKR3).
• To evaluate the utility of these probes in investigating ACKR3's function in cellular contexts.

Main Methods:

• Synthesis of a series of small molecule ACKR3 agonists.
• Development of fluorescent probes based on these agonists.
• Characterization using luminescence-based NanoBRET binding assays and confocal microscopy.

Main Results:

• Three fluorescent probes demonstrated specific binding to ACKR3 with high affinity (pKd 6.8–7.8).
• Probes were successfully applied in competition binding experiments.
• Cellular distribution of ACKR3 was visualized using confocal microscopy.

Conclusions:

• Novel fluorescent probes targeting ACKR3 have been successfully developed.
• These probes serve as valuable chemical tools for investigating ACKR3's role in cancer and other diseases.
• The probes facilitate cellular localization studies and binding assays, advancing research in chemokine receptor biology.