Design & Synthesis of Organic Compounds as Molecular Tools
To uncover basic principles of life at the molecular level, we are interested in detection and quantification of biomolecular activities. The key of this method is the development of chemical probes that can detect and report specific biomolecular events. In particular, we have recently developed FreSH (fluorescent real-time thiol) tracer and its derivatives for the reversible monitoring of intracellular glutathione (GSH) levels. Using these probes, we could show that high GSH levels are essential to maintain stem cell functions.
In addition, we are working toward rational design and synthesis of small-molecule enzyme inhibitors. Enzymes play pivotal roles in biological systems and many clinical disorders are closely associated with unregulated enzyme activities. Our study aims to develop enzyme inhibitors and use them as chemical tools to understand the biological functions of the targeted enzymes. Currently, we are trying to develop selective inhibitors of tissue transglutaminase, an enzyme responsible for protein-protein crosslinking reactions and ageing-related processes.
Also, we have successfully developed several chiral auxiliary reagents for the assignment of the absolute configuration of chiral molecules by NMR spectroscopy. Reagents with a conformational preference for intramolecular hydrogen bonding can produce significant anisotropic effects. As a result, large chemical shift changes can be induced on the chiral molecule attached, providing a reliable way to determine the absolute configuration.
In addition, we are working toward rational design and synthesis of small-molecule 