Calorimetric Characterisation of the Binding Reaction Between Human Ferric Haemoglobins and Haptoglobin to Develop a Drug for Removal of Cell-Free Haemoglobin

Khuanpiroon Ratanasopa, Leif Bulow

Research output: Chapter in Book/Report/Conference proceedingBook chapterResearchpeer-review

Abstract

High levels of cell-free haemoglobin (Hb) may occur in plasma as a consequence of e.g., pathological haemolysis or blood transfusion. These Hb molecules can be removed from blood circulation by forming a complex with the acute-phase protein haptoglobin (Hp) and thereby can also the intrinsic toxicity of free Hb be limited. In this study it is shown that ferric HbA, HbF, HbE and HbS, respectively, all bind firmly to Hp at 25 °C. By using isothermal titration calorimetry (ITC), it is demonstrated that ferric HbF has higher affinity to Hp (Ka = 2.79 ± 0.29 ×109 M−1) compared with HbA and HbS (1.91 ± 0.24 ×109 M−1) and 1.41 ± 0.34 ×109 M−1 for HbA and HbS, respectively. In addition, the affinity constant for HbE is slightly lower than the other haemoglobins (0.47 ± 0.40 ×109 M−1). Since Hp shows a general and high affinity to all Hb variants tested, it can be concluded that Hp may be useful as a therapeutic agent for several different haemolytic conditions by intravenous injection.

Original languageEnglish
Title of host publicationOxygen Transport to Tissue XLIII
PublisherSpringer Gabler
Pages341-345
Number of pages5
ISBN (Electronic)978-3-031-14190-4
ISBN (Print)978-3-031-14189-8
DOIs
Publication statusPublished - 2022

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1395
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Subject classification (UKÄ)

  • Biological Sciences
  • Hematology

Free keywords

  • Hb variants
  • Isothermal titration calorimetry
  • Pathological haemolysis
  • Sickle cell anemia

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