Peptidic Catalysts Conformationally Tuned for Fluoride Binding and Delivery
Gabija Poškaitė1, Thomas Schlatzer1, Zijun Chen1
1Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, United Kingdom.
Journal of the American Chemical Society
|February 24, 2026
Summary
Researchers experimentally show peptides can bind fluoride ions, leading to the first peptide-catalyzed fluorination reactions. This discovery opens new avenues for peptide-based catalysts in fluorination chemistry.
Area of Science:
- Biochemistry
- Organic Chemistry
- Catalysis
Background:
- Current knowledge on fluoride-peptide interactions is primarily based on computational (in silico) studies.
- Experimental data on peptide binding of fluoride ions is scarce.
Purpose of the Study:
- To experimentally investigate the binding capabilities of peptidic scaffolds with fluoride.
- To explore the potential of peptides as catalysts in fluorination reactions.
Main Methods:
- Utilized tetrabutylammonium fluoride trihydrate (TBAF·3H2O) and cesium fluoride (CsF) for fluoride binding experiments.
- Employed Nuclear Magnetic Resonance (NMR) spectroscopy and GOAT-DFT (Gradient-Optimized Approximate DFT) calculations for detailed analysis.
- Developed and tested peptide-catalyzed fluorination reactions.
Main Results:
- Demonstrated that specific peptidic scaffolds can effectively bind fluoride ions.
- NMR and GOAT-DFT studies revealed peptides acting as chelators for both fluoride and cesium ions when using CsF.
- Successfully developed the first peptide-catalyzed fluorination reactions, showcasing catalytic activity.
Conclusions:
- Peptides can experimentally bind fluoride ions, expanding beyond in silico predictions.
- Peptides can function as chelators for metal ions and fluoride, enabling novel catalytic applications.
- The development of peptide-catalyzed fluorination reactions represents a significant advancement in synthetic chemistry and catalyst design, potentially mimicking early enzymatic processes.
