Calorimetric Characterisation of the Binding Reaction Between Human Ferric Haemoglobins and Haptoglobin to Develop a Drug for Removal of Cell-Free Haemoglobin
(2022) In Advances in Experimental Medicine and Biology 1395. p.341-345- 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... (More)
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.
(Less)
- author
- Ratanasopa, Khuanpiroon LU and Bulow, Leif LU
- organization
- publishing date
- 2022
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- Hb variants, Isothermal titration calorimetry, Pathological haemolysis, Sickle cell anemia
- host publication
- Oxygen Transport to Tissue XLIII
- series title
- Advances in Experimental Medicine and Biology
- volume
- 1395
- pages
- 5 pages
- publisher
- Springer Gabler
- external identifiers
-
- pmid:36527659
- scopus:85144585279
- ISSN
- 2214-8019
- 0065-2598
- ISBN
- 978-3-031-14190-4
- 978-3-031-14189-8
- DOI
- 10.1007/978-3-031-14190-4_55
- language
- English
- LU publication?
- yes
- id
- 33302634-6125-4899-a076-ad61214e9cc1
- date added to LUP
- 2023-01-16 14:07:30
- date last changed
- 2024-04-03 18:25:43
@inbook{33302634-6125-4899-a076-ad61214e9cc1,
abstract = {{<p>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 ×10<sup>9</sup> M<sup>−1)</sup> compared with HbA and HbS (1.91 ± 0.24 ×10<sup>9</sup> M<sup>−1)</sup> and 1.41 ± 0.34 ×10<sup>9</sup> M<sup>−1</sup> for HbA and HbS, respectively. In addition, the affinity constant for HbE is slightly lower than the other haemoglobins (0.47 ± 0.40 ×10<sup>9</sup> M<sup>−1</sup>). 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.</p>}},
author = {{Ratanasopa, Khuanpiroon and Bulow, Leif}},
booktitle = {{Oxygen Transport to Tissue XLIII}},
isbn = {{978-3-031-14190-4}},
issn = {{2214-8019}},
keywords = {{Hb variants; Isothermal titration calorimetry; Pathological haemolysis; Sickle cell anemia}},
language = {{eng}},
pages = {{341--345}},
publisher = {{Springer Gabler}},
series = {{Advances in Experimental Medicine and Biology}},
title = {{Calorimetric Characterisation of the Binding Reaction Between Human Ferric Haemoglobins and Haptoglobin to Develop a Drug for Removal of Cell-Free Haemoglobin}},
url = {{http://dx.doi.org/10.1007/978-3-031-14190-4_55}},
doi = {{10.1007/978-3-031-14190-4_55}},
volume = {{1395}},
year = {{2022}},
}