Preparation and anticoagulant activity of the phosphosulfomannan PI-88

Eur J Med Chem. 2002 Oct;37(10):783-91. doi: 10.1016/s0223-5234(02)01347-8.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anticoagulants / chemical synthesis*
  • Anticoagulants / pharmacology*
  • Blood Coagulation Tests
  • Carbohydrate Sequence
  • Chromatography, Gel / methods
  • Dose-Response Relationship, Drug
  • Electrophoresis, Capillary
  • Humans
  • Mannans / chemistry
  • Mannans / pharmacology
  • Molecular Sequence Data
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / pharmacology*
  • Pichia / chemistry
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Anticoagulants
  • Mannans
  • Oligosaccharides
  • Protease Inhibitors
  • phosphomannopentaose sulfate
  • phosphomannan