Using “On/Off” ¹⁹F NMR/Magnetic Resonance Imaging Signals to Sense Tyrosine Kinase/Phosphatase Activity in Vitro and in Cell Lysates

Tyrosine kinase and phosphatase are two important, antagonistic enzymes in organisms. Development of noninvasive approach for sensing their activity with high spatial and temporal resolution remains challenging. Herein, we rationally designed a hydrogelator Nap-Phe-Phe­(CF₃)-Glu-Tyr-Ile-OH (<b>1a</b>) whose supramolecular hydrogel (i.e., Gel <b>1a</b>) can be subjected to tyrosine kinase-directed disassembly, and its phosphate precursor Nap-Phe-Phe­(CF₃)-Glu-Tyr­(H₂PO₃)-Ile-OH (<b>1b</b>), which can be subjected to alkaline phosphatase (ALP)-instructed self-assembly to form supramolecular hydrogel Gel <b>1b</b>, respectively. Mechanic properties and internal fibrous networks of the hydrogels were characterized with rheology and cryo transmission electron microscopy (cryo-TEM). Disassembly/self-assembly of their corresponding supramolecular hydrogels conferring respective “On/Off” ¹⁹F NMR/MRI signals were employed to sense the activity of these two important enzymes <i>in vitro</i> and in cell lysates for the first time. We anticipate that our new ¹⁹F NMR/magnetic resonance imaging (MRI) method would facilitate pharmaceutical researchers to screen new inhibitors for these two enzymes without steric hindrance