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Fixation of aldehydic dextrans onto human deoxyhemoglobin
Author(s) -
Klett D.,
Grandgeorge M.,
Dellacherie E.
Publication year - 1992
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360320507
Subject(s) - chemistry , hemoglobin , blood substitute , oxygen , dextran , allosteric regulation , glutaraldehyde , conjugate , polymer chemistry , polymerization , polymer , p50 , monomer , stereochemistry , biochemistry , chromatography , organic chemistry , enzyme , mathematical analysis , mathematics , transcription factor , gene
A procedure commonly used to transform native adult human hemoglobin (Hb) into a physiological oxygen carrier consists of a pyridoxylation of the protein to lower its oxygen affinity, followed by its polymerization in the presence of glutaraldehyde, with or without further reduction, to increase its circulating half‐life. This series of reactions yields derivatives presenting a great molecular heterogeneity that have to be fractionated for use in vivo. Hemoglobin derivatives with low oxygen affinity and a narrow distribution of molecular weights were obtained by linking a dextran polyaldehydic derivative to deoxyhemoglobin at pH 8. From oxygen‐binding measurements carried out in the presence of inositolhexaphosphate, a strong effector of hemoglobin, it appeared that the allosteric site of hemoglobin was blocked, probably by crosslinking bonds, which stabilizes its deoxy structure. On the other hand, when the reaction was performed in the presence of inositolhexaphosphate, the resulting conjugates exhibited an oxygen affinity identical to that of unmodified hemoglobin. After treatment with NaBH 4 , the polymer–hemoglobin derivatives were stable and possessed a reversible oxygen‐carrying capacity similar to that of blood. The conjugates prepared from oxyhemoglobin all possessed a lower P 50 than native hemoglobin whatever the reaction conditions.