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Nat Rev Drug Discov. 2004 Feb;3(2):152-9.

Oxygen therapeutics: can we tame haemoglobin?

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  • 1Laboratory of Biochemistry, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, National Institutes of Health, Bethesda, Maryland 20892, USA.


Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment--red blood cells--in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function.

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