title: Low anticoagulant heparin oligosaccharides as inhibitors of BACE-1, the Alzheimer's β-secretase.
abstract: Heparin (HP) is a promising agent for anti-Alzheimer's disease (AD), but its anticoagulant activity limits its applications. So a low anticoagulant heparin (LAH) with anti-AD effect is needed. A novel LAH and heparan sulfate (HS) were purified from crude porcine intestinal heparin. Their structures were characterized by nuclear magnetic resonance and liquid chromatography-mass spectrometry. LAH had a relatively high degree of sulfation, but lower than that of HP. 3-O-Sulfated-containing glucosamine residues further confirmed the low anticoagulant activity of LAH. Sixteen oligosaccharides of LAH and HS were prepared and assigned. Evaluation of anti-BACE-1 activities suggested that their potencies were positively correlated with degree of sulfation and polymerization of oligosaccharides. Besides, LAH-derived hexa- to dodecasaccharides was promised to be administrated in vitro as BACE-1 inhibitors. This study presented ideal BACE-1 inhibitors, LAH-derived oligosaccharides, with virtually no anticoagulant activities, which were promised to be excellent leads for treatment of AD.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Qinying
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cai
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China. Electronic address: liguoyun@ouc.edu.cn.
authors.forename: Guoyun
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237,China. Electronic address: glyu@ouc.edu.cn.
authors.forename: Guangli
authors.initials: G
authors.lastname: Yu
mesh_terms: D000544:Alzheimer Disease; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000925:Anticoagulants / Q000737:chemistry; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry*; D011516:Prothrombin / Q000737:chemistry
chemical_list: D000925:Anticoagulants; D009844:Oligosaccharides; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D053829:Amyloid Precursor Protein Secretases; D015951:Factor Xa; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Alzheimer’s disease; Anti-β-secretase-1 activities; Heparan sulfate; Low anticoagulant heparin; Oligosaccharide