Enlarging the scenario of site directed 19F labeling for NMR spectroscopy of biomolecules

The possibility of using selectively incorporated 19F nuclei for NMR spectroscopic studies has retrieved increasing interest in recent years. The high gyromagnetic ratio of 19F and its absence in native biomolecular systems make this nucleus an interesting alternative to standard 1H NMR spectroscopy. Here we show how we can attach a label, carrying a 19F atom, to protein tyrosines, through the use of a specific three component Mannich-type reaction. To validate the efficacy and the specificity of the approach, we tested it on two selected systems with the aid of ESI MS measurements.