What is our biological target? One of the problems currently being addressed in our group is the VDR. Nature provided its particular structure to the active vitamin D molecule to interact with the biological targets (VDR and some more else), and we first concentrate the form of the natural hormone to catch the key partial structures. Through rational design including stereochemistry based on organic and bioorganic chemistry, we synthesize efficiently the new analogues to create more potent and more selective ligands for the VDR. Biological evaluations inform us of fundamental structure-function relationships. The systematic modifications on the A-ring, especially at the C2 position, of 1a,25-dihydroxyvitamin D3 allowed us more biologically active analogues in terms of VDR binding affinity, induction of HL-60 cell differentiation and antiproliferative activity in several cancer cell lines without significant elevation of serum calcium concentration than the natural hormone.

Mode of actions of the ligands. Agonists of the VDR change conformation of the helix 12 of the receptor trough their docking. Based on this essential mechanism to initiate the target gene expression, we study potent antagonists of the VDR to treat for Paget's disease of bone. We also study specific ligands for a mutant VDR of hereditary vitamin D-resistant rickets (HVDRR), which is a genetic disorder caused by mutations in the VDR leading to resistance to the active vitamin D3.

Interaction of DNA(PNA) with DNA-binding proteins. From basic structural aspects, efforts have been devoted to elucidating interactions of single/double stranded DNA or PNA with DNA-binding proteins, Myb, NFkB, RecA, etc.

We consider making full use of knowledge of organic, synthetic organic, and bioorganic chemistry is very important on the grounds of studying medicinal chemistry and finding a seed of new medicine.