@article{3050777,
    title = "Modulating the oxygen affinity of human fetal haemoglobin with synthetic
allosteric modulators",
    author = "Papassotiriou, I and Kister, J and Griffon, N and Stamoulakatou, A and and Abraham, DJ and Marden, MC and Loukopoulos, D and Poyart, C",
    journal = "British Journal of Haematology",
    year = "1998",
    volume = "102",
    number = "5",
    pages = "1165-1171",
    publisher = "Blackwell Science Ltd Oxford, UK",
    issn = "0007-1048, 1365-2141",
    doi = "10.1046/j.1365-2141.1998.00886.x",
    keywords = "HbF; HbF-acetylated; beta-thalassaemia; allosteric modulators; tissue
oxygenation",
    abstract = "Improving the delivery of oxygen to the tissues by decreasing the oxygen
affinity of haemoglobin has been a major aim of several laboratories
over recent years because this may reduce the consequences of anaemia
and/or improve tissue oxygenation in cases of decreased blood perfusion.
Within the same context, lowering the oxygen affinity may prove valuable
in the application of native or recombinant haemoglobin solutions as a
blood substitute. The shift of the oxygen equilibrium curve to the right
is obtained by various modulators. Among them, the bezafibrate
derivatives are considered as a most interesting group. These principles
are of the utmost importance in thalassaemia and other
haemoglobinopathies where the beneficial effects of the compensatory
synthesis of fetal haemoglobin are diminished by the increased oxygen
affinity of this pigment. In this paper we present the results of a
study initiated to determine whether a potent oxygen affinity modifier,
RSR-4, could satisfactorily decrease the oxygen affinity of fetal
haemoglobin, thus improving tissue oxygenation. The experiments were
carried out on whole blood and on purified haemoglobin solutions and
showed that the effector markedly decreased the oxygen affinity of HbF
(from 18.7 to 37.3 mmHg in whole blood). At the same time the
cooperativity index (n(50)) and the oxygen saturation levels remained
within normal limits under the conditions of the main experiment. These
observations have important implications for the potential application
of oxygen affinity modifiers in vivo."
}