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Molecular imaging technologies, which enable the visualization of the behaviors or functions of biomolecules in living systems, have received considerable attention from life scientists. Novel imaging technologies that overcome the limitations of current imaging techniques are desired. In this review, two independent technologies that were recently developed by the authors are described. The first technology is for smart (19)F magnetic resonance imaging (MRI) probes that were developed for in vivo applications. These probes were developed by exploiting paramagnetic relaxation enhancement in order to detect hydrolase activity. With respect to cellular applications, gene expression in cells was visualized using one of the (19)F MRI probes. It was confirmed that this probe design principle is effective for various hydrolases, and broad applications are expected. The second technology is for practical protein labeling. This labeling method is based on a mutant β-lactamase and its specific labeling probes. Since the probe is fluorescence resonance energy transfer (FRET)-based, this labeling method achieves both specific and fluorogenic labeling of target proteins. In addition, derivatization of the probe enabled the labeling of intracellular proteins and the modification of various functional molecules.

Development of Molecular Imaging Tools to Investigate Protein Functions by Chemical Probe Design