title: Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells.
abstract: Glycosaminoglycans reportedly play important roles in prion formation, but because of their structural complexity, the chemical structures affecting prion formation have not been fully evaluated. Here, we compared two types of low molecular weight heparins and found that heparinase I-sensitive structures influenced anti-prion activity in prion-infected cells. Surface plasmon resonance analyses showed significant binding of a representative heparinase I substrate disaccharide unit, GlcNS6S-IdoA2S, to recombinant prion protein (PrP) fragments, such as full-length PrP23-231 and N-terminal domain PrP23-89, but not to PrP89-230. This binding was competitively inhibited by heparin or pentosan polysulfate, but not by Cu(2+). These PrP binding profiles of the disaccharide unit are consistent with those previously reported for heparin. However, synthetic compounds comprising disaccharide unit alone or its multimers exhibited no anti-prion activity in prion-infected cells. Consequently, the findings suggest that the heparin disaccharide unit that binds to the N-terminal region of PrP is a key structure, but it is insufficient for exerting anti-prion activity.
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Teruya
authors.affiliation: Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Kohrimoto, Kagoshima 890-0065, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wakao
authors.affiliation: Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Kohrimoto, Kagoshima 890-0065, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Hamanaka
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nishizawa
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Funayama
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakasegawa
authors.affiliation: Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Kohrimoto, Kagoshima 890-0065, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suda
authors.affiliation: Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Aoba-ku, Sendai 980-8575, Japan. Electronic address: doh-ura@med.tohoku.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Doh-ura
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004187:Disaccharides / Q000378:metabolism* / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D019763:Heparin Lyase / Q000378:metabolism*; D051379:Mice; D011328:Prions / Q000187:drug effects*
chemical_list: D004187:Disaccharides; D011328:Prions; D006493:Heparin; D019763:Heparin Lyase
keywords: Anti-prion; Glycosaminoglycan; Heparinase; Low molecular weight heparin; Prion; Surface plasmon resonance