Increasing haemoglobin oxygen affinity to prevent sickling: abnormal haemoglobin variants as models.
Two abnormal high oxygen affinity haemoglobins have been studied for their ability to inhibit the polymerization of deoxy-Hb S. They were used as models to predict the effect of chemically modifying haemoglobin to increase oxygen affinity since the oxy(R)-conformation is the most potent inhibitor known of cell sickling. The participation of these variants in deoxy-Hb S polymers has been described quantitatively in terms of an exclusion coefficient, f, that relates their behaviour to that of deoxy-Hb S, and qualitatively in terms of an exponent of hybridization. Hb Bethesda was a potent inhibitor of polymerization, its behaviour being similar to that of Hb F studied previously. Hb Radcliffe demonstrated atypical behaviour, with hybrid molecules of the formula alpha 2 beta S beta Rad participating in the polymerization as effectively as Hb S, as has been shown for Hb C. These data have implications for the development of anti-sickling agents designed to increase oxygen affinity by covalent binding to Hb S.
D000755:Anemia, Sickle Cell / Q000378:metabolism*; D000986:Antisickling Agents / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D010100:Oxygen / Q000378:metabolism*; D012805:Sickle Cell Trait / Q000378:metabolism*
D000986:Antisickling Agents; D006451:Hemoglobin, Sickle; D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; C038875:deoxyhemoglobin, sickle; C050911:hemoglobin Bethesda; C050912:hemoglobin Radcliffe; D010100:Oxygen