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Hematol Oncol Clin North Am. 2014 Apr;28(2):217-31. doi: 10.1016/j.hoc.2013.11.001. Epub 2014 Jan 21.

Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin.

Author information

1
Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, School of Pharmacy, Virginia Commonwealth University, 800 E. Leigh Street, P.O. Box 980540, Richmond, VA 23219-1540, USA.
2
Division of Hematology-Oncology, Department of Medicine, Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, 200 Lothrop Street, BST E1240, Pittsburgh, PA 15261, USA. Electronic address: katogj@upmc.edu.

Abstract

The pathophysiology of sickle cell disease involves the polymerization of sickle hemoglobin in its T state, which develops under low oxygen saturation. One therapeutic strategy is to develop pharmacologic agents to stabilize the R state of hemoglobin, which has higher oxygen affinity and is expected to have slower kinetics of polymerization, potentially delaying the sickling of red cells during circulation. This strategy has stimulated the investigation of aromatic aldehydes, aspirin derivatives, thiols, and isothiocyanates that can stabilize the R state of hemoglobin in vitro. One representative aromatic aldehyde agent, 5-hydoxymethyl-2-furfural, protects sickle cell mice from the effects of hypoxia.

KEYWORDS:

5-HMF; Antisickling; Hemoglobin allosteric effectors; R state; Sickle cell

PMID:
24589263
PMCID:
PMC4195245
DOI:
10.1016/j.hoc.2013.11.001
[Indexed for MEDLINE]
Free PMC Article
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