Precise transplant of biomolecule to synthesized molecule -Cyborg supramolecule to reveal the origin of pathogenetic materials-



Sota Sato, Yutaka Yoshimasa, Daishi Fujita, Maho Yagi-Utsumi, Takumi Yamaguchi, Koichi Kato, and Makoto Fujita



 The research group of Prof. Makoto Fujita in Department of Applied Chemistry, School of Engineering, the University of Tokyo, Prof. Koichi Kato in Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences/Institute for Molecular Science, and Associate Prof. Sota Sato in WPI-AIMR, Tohoku University succeeded in the self-assembly of a sugar cluster with a sophisticated molecular design. The self-assembly of organic molecules and transition-metal ions afforded a well-defined, world’s largest spherical molecule just by mixing the starting materials.
(ref. the previous press release from the University of Tokyo ).

The research group hybridized the sugar parts of biological origin to an artificially synthesized self-assembled supramolecule, and succeeded in the construction of a cyborg supramolecule. The hydrophobic environment traps a cohesive protein, and the interaction between the cohesive protein and a sugar cluster is not observable in the system. Therefore, the research group designed the cyborg supramolecule by tethering the sugar part of ganglioside GM1 with the removal of hydrophobic part to the spherical molecule bearing no hydrophobic environment like cellular membrane. With the synthetic strategy, the sugar cluster of ganglioside GM1 was constructed with the precisely controlled structure: the number and position of sugar moieties are defined, and the surface curvedness was uniform over the molecule (See the Figure). For the sample solution of the sugar cluster and an amyloid  β  protein, the Nuclear Magnetic Resonance (NMR) analysis revealed the selective recognition of N-terminal of the protein. For another cohesive protein, α-synuclein, which is known to be involved in the pathogenic pathway of Parkinson's Disease, the recognition mechanism was also revealed in detail. The transplant of biological sugar cluster to a well-defined artificial molecule with the retention of the original biological function realized the high-resolution analysis to reveal undiscovered mechanism in vital phenomena.