Enhanced aqueous Suzuki-Miyaura coupling allows site-specific polypeptide 18F-labeling

Area of Science:

• Radiochemistry
• Organic Chemistry
• Biochemistry

Background:

• Protein labeling often requires specific conditions that are incompatible with standard chemical reagents.
• Efficient radiolabeling, especially with isotopes like fluorine-18, faces challenges with reagent stoichiometry.

Purpose of the Study:

• To develop a novel catalyst system for efficient aqueous Suzuki-Miyaura cross-coupling.
• To enable site-specific radiolabeling of biomolecules, including proteins, using fluorine-18.

Main Methods:

• Screening of aqueous palladium(0) ligand systems.
• Identification of 1,1-dimethylguanidine as an effective ligand.
• Application of the novel catalyst for radiolabeling with [(18)F]4-fluorophenylboronic acid.

Main Results:

• Discovery of 1,1-dimethylguanidine as a superior ligand for aqueous Suzuki-Miyaura cross-coupling.
• Successful labeling of small molecules, peptides, and proteins with fluorine-18.
• Demonstration of site-specific protein (18)F-labeling.

Conclusions:

• A novel palladium catalyst system enables efficient and site-specific protein (18)F-labeling.
• The metal-triggered reaction operates under biologically compatible conditions.
• This advancement facilitates the use of fluorine-18 radiolabeling in biological and medical applications.