Seeking “Etwas Neues”—From Bioorganic Chemistry to Alzheimer's Disease—

Abstract

Introduction to bioorganic chemistry by Prof. Kanaoka at the entrance of my research works affects greatly throughout the life afterward. Chemical modification studies of enzyme proteins taught me quality of chemical reactions. For example, triethyloxonium fluoroborate (Et3O+ BF4(-)), a Meerwein reagent, selectively reacted with a particular carboxyl group (Asp-177) in the substrate binding site of trypsin, even though the reaction was performed in aqueous solution. A series of ion channel studies intoxicate me how exciting the science works are. Purification of sodium channel protein from electric eels initiated the collaboration work to reveal total primary structure of the molecule, as an inaugurating work of ion channel molecules. Photoaffinity labeling proved to be an efficient method to elucidate ligand binding sites, such as TTX binding site within the sodium channel and the sites for calcium anatagonists in L-type calcium channels. Encounter with CD36 molecule expands our works to more pathobiochemical field. We revealed CD36, a class B scavenger receptor, is related to development of atherosclerosis by phagocytosis of ox-LDL in macrophages and even matured adipocytes. In microglia, however, CD36 plays clearance role of oligomeric beta-amyloid peptides in IL-4 activated type-2 microglia, suggesting the activation of type-2 microglia may be useful for developing a new method to treat or prevent from Alzheimer's disease.