title: Heparin dodecasaccharide containing two antithrombin-binding pentasaccharides: structural features and biological properties.
abstract: The antithrombin (AT) binding properties of heparin and low molecular weight heparins are strongly associated to the presence of the pentasaccharide sequence AGA*IA (A(NAc,6S)-GlcUA-A(NS,3,6S)-I(2S)-A(NS,6S)). By using the highly chemoselective depolymerization to prepare new ultra low molecular weight heparin and coupling it with the original separation techniques, it was possible to isolate a polysaccharide with a biosynthetically unexpected structure and excellent antithrombotic properties. It consisted of a dodecasaccharide containing an unsaturated uronate unit at the nonreducing end and two contiguous AT-binding sequences separated by a nonsulfated iduronate residue. This novel oligosaccharide was characterized by NMR spectroscopy, and its binding with AT was determined by fluorescence titration, NMR, and LC-MS. The dodecasaccharide displayed a significantly increased anti-FXa activity compared with those of the pentasaccharide, fondaparinux, and low molecular weight heparin enoxaparin.
authors.affiliation: Sanofi, 13 Quai Jules Guesde, 94403 Vitry sur Seine, France, and.
authors.forename: Christian
authors.initials: C
authors.lastname: Viskov
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Elli
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Urso
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gaudesi
authors.affiliation: Sanofi, 13 Quai Jules Guesde, 94403 Vitry sur Seine, France, and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mourier
authors.affiliation: Sanofi, 13 Quai Jules Guesde, 94403 Vitry sur Seine, France, and.
authors.forename: Frederic
authors.initials: F
authors.lastname: Herman
authors.affiliation: the Laboratoire de Biophotonique et Pharmacologie, UMR CNRS 7213, Faculté de Pharmacie, Université de Strasbourg, F67401 Illkirch, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Boudier
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy.
authors.forename: Benito
authors.initials: B
authors.lastname: Casu
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy.
authors.forename: Giangiacomo
authors.initials: G
authors.lastname: Torri
authors.affiliation: From the Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', via G. Colombo 81, 20133 Milan, Italy,. Electronic address: guerrini@ronzoni.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Guerrini
mesh_terms: D002240:Carbohydrate Sequence; D015951:Factor Xa / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry; D006493:Heparin; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D005343:Fibrinolytic Agents; D009844:Oligosaccharides; D006493:Heparin; D015951:Factor Xa
keywords: 3-O-Sulfation; Antithrombin; Glycosaminoglycan; Heparin; Mass Spectrometry (MS); NMR