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Increasing haemoglobin oxygen affinity to prevent sickling: abnormal haemoglobin variants as models
Author(s) -
Franklin I. M.,
Huehns E. R.,
Rosemeyer M. A.
Publication year - 1986
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1986.tb04125.x
Subject(s) - polymerization , chemistry , oxygen , stereochemistry , hemoglobin , polymer , biochemistry , organic chemistry
S ummary . 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 α 2 β s β 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.