Therapeutic strategies to alter the oxygen affinity of sickle hemoglobin

Martin K. Safo, Gregory J. Kato

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)217-231
Number of pages15
JournalHematology/Oncology Clinics of North America
Issue number2
StatePublished - Apr 2014
Externally publishedYes


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

ASJC Scopus subject areas

  • Hematology
  • Oncology


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