title: Fixation of aldehydic dextrans onto human deoxyhemoglobin.
abstract: 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 NaBH4, 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 P50 than native hemoglobin whatever the reaction conditions.
authors.affiliation: Laboratoire de Chimie-Physique Macromoléculaire, URA CNRS 494, ENSIC, Nancy, France.
authors.forename: D
authors.initials: D
authors.lastname: Klett
authors.forename: M
authors.initials: M
authors.lastname: Grandgeorge
authors.forename: E
authors.initials: E
authors.lastname: Dellacherie
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D003911:Dextrans / Q000378:metabolism*; D006441:Hemoglobin A / Q000378:metabolism*; D006801:Humans; D010108:Oxyhemoglobins / Q000378:metabolism; D010833:Phytic Acid / Q000494:pharmacology; D011485:Protein Binding
chemical_list: D000447:Aldehydes; D003911:Dextrans; D010108:Oxyhemoglobins; D010833:Phytic Acid; D006441:Hemoglobin A; C029774:oxyhemoglobin A