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Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin.

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.

SUBMITTER: Safo MK

PROVIDER: S-EPMC4195245 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin.

Safo Martin K MK Kato Gregory J GJ

Hematology/oncology clinics of North America 20140121 2

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 ...[more]

PMID: 24589263

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