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-...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2002-10, Vol.37 (10), p.783-791
Main Authors: Yu, Guangli, Gunay, Nur Sibel, Linhardt, Robert J, Toida, Toshihiko, Fareed, Jawed, Hoppensteadt, Debra A, Shadid, Hazar, Ferro, Vito, Li, Caiping, Fewings, Kym, Palermo, Maria C, Podger, Denis
Format: Article
Language:English
Subjects:
anticoagulant
Anticoagulants - chemical synthesis
Anticoagulants - pharmacology
Biological and medical sciences
Blood Coagulation Tests
Blood. Blood coagulation. Reticuloendothelial system
capillary electrophoresis
Carbohydrate Sequence
Chromatography, Gel - methods
Dose-Response Relationship, Drug
Electrophoresis, Capillary
Humans
Mannans - chemistry
Mannans - pharmacology
Medical sciences
Molecular Sequence Data
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular - methods
Oligosaccharides - chemical synthesis
Oligosaccharides - pharmacology
Pharmacology. Drug treatments
phosphomannan
phosphosulfomannan
PI-88
Pichia - chemistry
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Spectrometry, Mass, Fast Atom Bombardment
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/S0223-5234(02)01347-8