Bioorganic-inorganic Chemistry

Our research group is interested in the bioorganic and bioinorganic chemistry of synthetic functional molecules. Using a combination of synthesis, NMR, UV, fluorometry, and computer modeling, we design and evaluate the compounds which perform certain functions and tasks. These molecules include the potential pharmaceuticals, such as antioxidants and Alzheimer’s drugs. Through these studies, we seek the new and general concept for the design of functional molecules. Our specific interests are listed below.

(1) Development and Evaluation of Cytochrome P450 Mimics. We have developed SR complex, which is a unique synthetic model of P450. This complex is the only synthetic heme-thiolate, which can retain thiolate axial coordination during catalytic oxidation reaction. Our research interest is revealing the role of thiolate ligand in P450 catalysis by using SR complex. We have also developed ruthenium porphyrin － heteroaromatic N-oxide system that is a robust oxidizing system for alkane, arene and N-acyl cyclic amine oxidation.

(2) ”Evolutionary Principles” Applied to Functional Organic Molecules. In this system, molecular diversity is generated by reversible covalent self-assembly of basic components. All library members are interconverting to give a distribution that is under thermodynamic control. By the addition of a “target” molecule, the equilibrium will shift in favor of the best binders at the expense of the poor receptors: amplification of the fittest is occurred as if “molecular evolution”. This concept is also known as ”dynamic combinatorial chemistry”, although we found this strategy independently.

(3) Novel Fluorescence Assay for Protein Kinases. We recently developed an on-bead fluorescence assay for serine/threonine kinases, utilizing the specific chemical reactivity of phosphoserine and phosphothreonine residues. This method can be applied to peptide-array which is suitable for high-throughput format.