Journal article
Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation
Biophysical journal
02 Jun 2023
Abstract
The drug voxelotor (commercially known as Oxbryta) has been approved by the Food and Drug Administration for the treatment of sickle cell disease. It is known to reduce disease-causing sickling by inhibiting the transformation of the non-polymerizing, high oxygen affinity R quaternary structure of sickle hemoglobin (HbS) into its polymerizing, low affinity T quaternary structure. It has not been established whether the binding of the drug has anti-sickling effects beyond restricting the change of quaternary structure. By using a laser photolysis method that employs microscope optics, we have determined that fully deoxygenated HbS will assume the T-structure. We show that the nucleation rates essential to generate the sickle fibers are not significantly affected by voxelotor. The method employed here should be useful for determining the mechanism of sickling inhibition for proposed drugs.
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Details
- Title
- Voxelotor does not inhibit sickle hemoglobin fiber formation upon complete deoxygenation
- Creators
- Eli H. Worth - Department of Physics, Drexel University, Philadelphia, PA 19104, USAMark K. Fugate - Department of Physics, Drexel University, Philadelphia, PA 19104, USAFrank A. Ferrone - Department of Physics, Drexel University, Philadelphia, PA 19104, USA
- Publication Details
- Biophysical journal
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Scopus ID
- 2-s2.0-85162179022
- Other Identifier
- 991020596268904721