Targeting monocarboxylate transporter 1 with a copper-chelating coumarin-based bioconjugate: Synthesis and...

Area of Science:

• Bioconjugate Chemistry
• Molecular Oncology
• Radiopharmaceutical Science

Background:

• Monocarboxylate Transporters (MCTs), especially MCT1, are vital in cancer metabolism and tumor progression.
• Overexpressed MCTs in cancers present therapeutic and diagnostic targets.

Purpose of the Study:

• To design, synthesize, and characterize a novel chimeric bioconjugate, LCPn.
• To integrate an MCT1-targeting moiety with a copper-chelating platform for potential theranostic applications.

Main Methods:

• Strategic synthesis involving macrocycle protection and SN2 coupling.
• Structural confirmation using NMR and mass spectrometry.
• Determination of protonation constants and metal-to-ligand complexation studies (Cu2+, Zn2+).
• Electrochemical analysis via cyclic voltammetry.
• In silico docking simulations and in vitro cell-based assays.

Main Results:

• Successful synthesis and characterization of the LCPn bioconjugate.
• LCPn forms stable 1:1 complexes with Cu2+ and Zn2+.
• The coumarin moiety shows high affinity for MCT1, inhibiting lactate uptake in prostate cancer models.
• Demonstrated dual functionality as an MCT1-targeting agent and a copper-chelating platform.

Conclusions:

• LCPn is a versatile bioconjugate with selective MCT1 targeting and robust copper-binding capabilities.
• This compound holds promise for developing novel inorganic bioconjugate-based theranostics in oncology.
• Further research can explore its application in targeted cancer therapy and diagnostics.