title: Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory activity.
abstract: The glycopolymers for glycosaminoglycan mimic were synthesized, and the inhibitory effects of Alzheimer's β-secretase (BACE-1) were examined. The regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The glycopolymers were synthesized with acrylamide using radical initiator. The glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1, and the inhibitory effects were dependent on the sulfation positions. Especially, glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect. The docking simulation suggested that glycopolymers bind to the active site of BACE-1.
authors.affiliation: Department of Chemical Engineering, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shudo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Seto
authors.forename: Yu
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Miura
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D006025:Glycosaminoglycans; D013431:Sulfates; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D000117:Acetylglucosamine
keywords: BACE-1; Glycopolymer; Glycosaminoglycan