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Related Experiment Videos

Hemoglobin tetramers stabilized with polyaspirins.

E Bucci1, C Fronticelli, A Razynska

  • 1Dept of Biochemistry, University of Maryland Medical School, Baltimore 21201.

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

Novel hemoglobin derivatives were created as potential oxygen carriers. These modified hemoglobins show stable structures and maintain normal physiological functions in animal models, offering promising blood substitute options.

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Area of Science:

  • Biochemistry
  • Biomaterials Science
  • Physiology

Background:

  • Hemoglobin (Hb) is a primary oxygen carrier in red blood cells.
  • Developing acellular Hb-based oxygen carriers (HBOCs) faces challenges like tetramer dissociation and renal toxicity.
  • Site-specific chemical modification of Hb can improve its properties as an HBOC.

Purpose of the Study:

  • To synthesize and characterize novel, stabilized hemoglobin derivatives using organic acids activated by esterification.
  • To evaluate the oxygen-binding properties (P50), stability, and physiological effects of these modified hemoglobins.
  • To assess the potential of these derivatives as blood substitutes.

Main Methods:

  • Esterification of organic acids with 3,5-dibromosalicylate to create polysapirins.

Related Experiment Videos

  • Site-specific crosslinking of human and bovine hemoglobin at beta 82 or alpha 99 lysines.
  • Purification of derivatives using column chromatography.
  • Assessment of oxygen affinity (P50) and stability against dimer dissociation.
  • In vivo studies involving infusion in rats and cats for renal, cardiac, and cerebral blood flow evaluation.

    • Main Results:

    • A family of hemoglobin derivatives with P50 values ranging from 10 to 50 mmHg was successfully constructed.
    • The derivatives are stabilized tetramers, resistant to dissociation into dimers.
    • Tri-(3,5-dibromosalicyl)-benzenetricarboxylate crosslinks Hb across beta subunits, decreasing oxygen affinity but preserving the Bohr effect.
    • In vivo infusions up to 50% blood replacement showed no adverse renal or cardiac effects.
    • Cerebral blood flow remained normal in cats during isovolemic hemodilution when using the oxygen carrier.

    Conclusions:

    • Esterified organic acids provide versatile and site-specific crosslinking of hemoglobin.
    • Stabilized hemoglobin tetramers exhibit favorable oxygen-carrying properties and stability.
    • These modified hemoglobins demonstrate safety and efficacy in preclinical animal models, indicating potential as blood substitutes.