Fluorinated Tags to Study Protein Conformation and Interactions Using ¹⁹F NMR

Area of Science:

• Biochemistry
• Biophysics
• Chemical Biology

Background:

• Fluorine-19 Nuclear Magnetic Resonance (19F NMR) serves as a sensitive reporter for biomolecular structure, conformation, and interactions.
• Incorporating fluorine atoms into biomolecules offers background-free detection and environmental sensitivity.

Purpose of the Study:

• This review discusses advancements in introducing fluorinated tags into biomolecules for NMR studies.
• It focuses on post-translational bioconjugation strategies, also known as 'fluorine-tagging'.

Main Methods:

• Synthetic incorporation via solid-phase peptide synthesis.
• Supplementing growth media with fluorinated amino acids during protein expression.
• Genetic code expansion to incorporate novel fluorinated amino acids.

Main Results:

• Exploration of various chemical tagging 'warheads' for fluorine incorporation.
• Discussion of diverse applications of fluorine tags in biomolecular studies.
• Strategies for enhancing reporter sensitivity and signal-to-noise ratios.

Conclusions:

• Fluorine-tagging presents a powerful approach for biomolecular NMR analysis.
• Future directions include addressing current challenges and further optimizing sensitivity and applications.