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Targeting HbS Polymerization
Journal article   Peer reviewed

Targeting HbS Polymerization

Frank A. Ferrone
Seminars in hematology, v 55(2)
Apr 2018
PMID: 30616807

Abstract

Allostery Anti-sickling drugs Kinetics Oxygen delivery Polymer structure Vaso-occlusion
The mutation of β6 from glu to val in hemoglobin is responsible for the polymer formation that leads to vaso-occlusion, and a range of severe consequences in sickle cell disease. The treatment of the disease can be addressed in many ways, but the prevention of polymer formation is one of the most fundamental approaches one can take. Such prevention includes affecting the polymer structure, or dilution of the fraction of polymerizable hemoglobin. The latter approach includes (1) induction of HbF, which does not itself, nor in hybrid form, join sickle polymers, or (2) restricting the allosteric change in hemoglobin that occurs in oxygen delivery, and which is required for polymer formation. These approaches will be critically reviewed, as well as the most recent developments that show the benefits of simply swelling the volume of the red cell.

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Hematology
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