title: Preparation and anticoagulant activity of the phosphosulfomannan PI-88.
abstract: A yeast-derived phosphomannan mixture was chemically sulfonated and the composition and structure of the product mixture was studied. This phosphosulfomannan mixture, PI-88, is currently under clinical evaluation as an anti-cancer agent. Analysis using capillary electrophoresis demonstrated that PI-88 was a multi-component mixture. Gel permeation chromatography provided four fractions of PI-88 that contained components which differed in size from disaccharide to hexasaccharide, and by degree of sulfation. These fractions were characterised by spectroscopic and chromatographic methods and the structure of PI-88 is that expected based on the structure of the phosphomannan starting material. The anticoagulant activity of these fractions was evaluated and the structural requirements for activity are described.
authors.affiliation: Department of Chemistry, Division of Medicinal and Natural Products Chemistry, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Guangli
authors.initials: G
authors.lastname: Yu
authors.forename: Nur Sibel
authors.initials: NS
authors.lastname: Gunay
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.forename: Debra A
authors.initials: DA
authors.lastname: Hoppensteadt
authors.forename: Hazar
authors.initials: H
authors.lastname: Shadid
authors.forename: Vito
authors.initials: V
authors.lastname: Ferro
authors.forename: Caiping
authors.initials: C
authors.lastname: Li
authors.forename: Kym
authors.initials: K
authors.lastname: Fewings
authors.forename: Maria C
authors.initials: MC
authors.lastname: Palermo
authors.forename: Denis
authors.initials: D
authors.lastname: Podger
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D002240:Carbohydrate Sequence; D002850:Chromatography, Gel / Q000379:methods; D004305:Dose-Response Relationship, Drug; D019075:Electrophoresis, Capillary; D006801:Humans; D008351:Mannans / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010843:Pichia / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000925:Anticoagulants; D008351:Mannans; D009844:Oligosaccharides; D011480:Protease Inhibitors; C120158:phosphomannopentaose sulfate; C005437:phosphomannan