Preparation and anticoagulant activity of the phosphosulfomannan PI-88.
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.
Yu
Guangli
G
Department of Chemistry, Division of Medicinal and Natural Products Chemistry, University of Iowa, Iowa City, IA 52242, USA.
Gunay
Nur Sibel
NS
Linhardt
Robert J
RJ
Toida
Toshihiko
T
Fareed
Jawed
J
Hoppensteadt
Debra A
DA
Shadid
Hazar
H
Ferro
Vito
V
Li
Caiping
C
Fewings
Kym
K
Palermo
Maria C
MC
Podger
Denis
D
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
D000925:Anticoagulants; D008351:Mannans; D009844:Oligosaccharides; D011480:Protease Inhibitors; C120158:phosphomannopentaose sulfate; C005437:phosphomannan