Pentafluorophosphato-Phenylalanines: Amphiphilic Phosphotyrosine Mimetics Displaying Fluorine-Specific Protein Interactions
Angew. Chem. Int. Ed.
News from May 05, 2022
Phosphotyrosine residues are essential functional switches in health and disease. Thus, phosphotyrosine biomimetics are crucial for the development of chemical tools and drug molecules. We report here the discovery and investigation of pentafluorophosphato-amino acids as novel phosphotyrosine biomimetics. The novel motifs bind 25- to 30-fold stronger to the phosphotyrosine binding site of the protein tyrosinephosphatase PTP1B than the best current biomimetics. Using computational methods, including molecular-dynamics simulations, we rationalize these findings