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Preparation and anticoagulant activity of the phosphosulfomannan PI-88
Guangli Yu1, Nur Sibel Gunay, Robert J Linhardt
1Department of Chemistry, Division of Medicinal and Natural Products Chemistry, University of Iowa, Iowa City, IA 52242, USA.
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.