A research group led by Associate Professor Haruhiko Fuwa and Professor Makoto Sasaki at Graduate School of Life Science, Tohoku University has designed and synthesized truncated analogues of a marine polycyclic ether natural product gambierol, and has revealed that these artificial compounds elicited voltage-gated potassium ion channel inhibitory activity equipotent to the natural product, in collaboration with a research group led by Professor Luis M. Botana at University of Santiago de Compostela. Furthermore, in primary cultured neurons of triple-transgenic mice, they have observed that gambierol and its truncated analogues decreased amyloid βpeptides and hyperphosphorylated tau proteins, which are believed to be responsible for Alzheimer's disease. This study is a pioneering work on the design and synthesis of novel biofunctional molecules based on the structural motif of polycyclic ether natural products. This achievement has been published in Journal of the American Chemical Society on May 2, 2012. The paper's title is "Design and Synthesis of Skeletal Analogues of Gambierol: Attenuation of Amyloid and Tau Pathology with Voltage-Gated Potassium Channel and N-Methyl-D-Aspartate Receptor Implications".
(About the research)
Associate Professor Haruhiko Fuwa
Biostructural Chemistry Laboratory
Graduate School of Life Science, Tohoku University
E-mail: hfuwa*bios.tohoku.ac.jp (Replace * with @)