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Related Experiment Videos

Hemoglobin linked to polyanionic polymers as potential red blood cell substitutes.

E Dellacherie1, M Grandgeorge, F Prouchayret

  • 1Laboratoire de Chimie-Physique Macromoléculaire, URA CNRS 494, ENSIC, Nancy, France.

Biomaterials, Artificial Cells, and Immobilization Biotechnology : Official Journal of the International Society for Artificial Cells and Immobilization Biotechnology
|January 1, 1992
PubMed
Summary

Chemically modified hemoglobin (Hb) using functionalized polymers like dextran and polyoxyethylene lowers oxygen affinity and reduces renal excretion, creating potential cell-free oxygen carriers for blood substitutes.

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Area of Science:

  • Biochemistry
  • Polymer Chemistry
  • Biomaterials Science

Background:

  • Cell-free hemoglobin (Hb) requires modifications for use as an oxygen carrier.
  • Modifications aim to increase Hb's plasma half-life and decrease oxygen affinity.
  • Polymer functionalization offers a strategy to achieve these desired properties.

Purpose of the Study:

  • To design and synthesize Hb derivatives with enhanced properties for use as blood substitutes.
  • To create covalent conjugates of Hb with functionalized polymers (dextran, polyoxyethylene).
  • To evaluate the impact of these modifications on oxygen affinity and pharmacokinetic properties.

Main Methods:

  • Covalent attachment of benzene hexacarboxylate (BHC) or benzene tetracarboxylate (BTC) functionalized polymers to oxyhemoglobin (oxyHb).

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  • Characterization of resulting Hb-polymer conjugates, including oxygen binding affinity and molecular weight.
  • Optimization of reaction parameters for dextran-linked benzene tetracarboxylate (dex-BTC) conjugates.

    • Main Results:

    • Polymer-Hb conjugates exhibited lower oxygen affinity compared to native Hb.
    • Polymer-linked BHC preferentially bound to beta-terminal valine residues, reducing oxygen affinity.
    • Optimization of dex-BTC conjugation yielded products suitable for in-vivo studies, with controlled viscosity and oncotic pressure.

    Conclusions:

    • Functionalized polymers effectively modify Hb properties for potential blood substitute applications.
    • The density of anionic groups and specific binding interactions are key to modulating oxygen affinity.
    • Optimized Hb-polymer conjugates show promise for further in-vivo evaluation as cell-free oxygen carriers.