title: A Self-Assembled Spherical Complex Displaying a Gangliosidic Glycan Cluster Capable of Interacting with Amyloidogenic Proteins.
abstract: Physiological and pathological functions of glycans are promoted through their clustering effects as exemplified by a series of gangliosides, sialylated glycosphingolipids, which serve as acceptors for bacterial toxins and viruses. Furthermore, ganglioside GM1 clusters on neuronal cell membranes specifically interact with amyloidogenic proteins, triggering their conformational transitions and leading to neurodegeneration. Here we develop a self-assembled spherical complex that displays a cluster of the GM1 pentasaccharide, and successfully demonstrate its ability to interact with amyloid β and α-synuclein. Due to the lack of hydrophobic lipid moieties, which would stably trap these cohesive proteins or give rise to toxic aggregates, this artificial cluster enabled NMR spectroscopic characterization of the early encounter stage of protein interactions with its outer carbohydrate moieties, which were not observable with previous glycan clusters.
authors.affiliation: Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan). satosota@m.tohoku.ac.jp.|Current address: WPI-AIMR, Tohoku University (Japan). satosota@m.tohoku.ac.jp.
authors.forename: Sota
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan).
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshimasa
authors.affiliation: Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan).
authors.forename: Daishi
authors.initials: D
authors.lastname: Fujita
authors.affiliation: Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science and Department of Bioorganization Research, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 (Japan).
authors.forename: Maho
authors.initials: M
authors.lastname: Yagi-Utsumi
authors.affiliation: Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science and Department of Bioorganization Research, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 (Japan).
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Life and Coordination-Complex Molecular Science, Institute for Molecular Science and Department of Bioorganization Research, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787 (Japan). kkato@phar.nagoya-cu.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan). mfujita@appchem.t.u-tokyo.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujita
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001665:Binding Sites; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D005677:G(M1) Ganglioside
keywords: NMR spectroscopy; amyloid β; self-assembly; sugar cluster; α-synuclein