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Engineered bio-active polysaccharides from heparin.

Scott E Guimond1, Jeremy E Turnbull, Edwin A Yates

  • 1School of Biological Sciences, University of Liverpool, L69 7ZB, UK.

Macromolecular Bioscience
|August 2, 2006
PubMed
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Modified heparin polysaccharides were engineered to enhance specific biological activities. One derivative showed significantly improved pro-angiogenic effects with greatly reduced anticoagulant properties, offering potential for medical applications.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Biotechnology

Background:

  • Heparin, a polysaccharide, interacts with various biological systems due to its similarity to heparan sulfate (HS).
  • Heparin's high sulfation often leads to a lack of selectivity in its biological activities.
  • Modifying heparin's structure can alter its properties and biological functions.

Purpose of the Study:

  • To engineer modified heparin polysaccharides with altered biological activities.
  • To investigate the effects of these derivatives on cell signaling pathways, specifically the FGF/FGFR system.
  • To assess the pro-angiogenic and anticoagulant properties of modified heparins.

Main Methods:

  • Chemical modifications of heparin including de-O-sulfation, de-N-sulfation, and re-N-acetylation.

Related Experiment Videos

  • In vitro cell assays using combinations of FGF ligands (FGF-1, -2, -3) and FGFRs (FGFR1, FGFR3).
  • Quantification of anticoagulant activity and assessment of pro-angiogenic effects, particularly FGF-2-mediated angiogenesis.

    • Main Results:

    • Modified heparin polysaccharides exhibited varied abilities to promote cell signaling via the FGF/FGFR pathway.
    • One derivative, N-acetylated, 6-O- and 2-O-sulfated heparin, retained minimal anticoagulant activity (<10(-3) of heparin).
    • This derivative demonstrated a 10-fold increase in FGF-2-mediated angiogenesis, yielding an improved activity ratio exceeding 10(4).

    Conclusions:

    • Heparin-derived polysaccharides can be chemically engineered to achieve selective biological activities.
    • These engineered heparins show potential for applications in medicine, biotechnology, and tissue engineering.
    • Targeted modification offers a strategy to enhance desired functions like angiogenesis while minimizing unwanted effects like anticoagulation.