Human hemoglobin conjugated to carboxylate dextran as a potential red blood cell substitute. I. Further physico-chemical characterization.
In a previous paper, we described the preparation of a conjugate by reaction of benzene tetracarboxylate-substituted dextran (dex-BTC) with oxyhemoglobin. The first biological experiments carried out on animals showed that a solution of this type of product could be regarded as an oxygen-carrying fluid. The physico-chemical properties of this conjugate have been further characterized in view of its potential application in clinical experiments. Its molecular size distribution and the fraction of intramolecularly cross-linked hemoglobin were determined by elution on various types of chromatographic columns. Moreover the conjugate's oxygen-binding properties were studied in the presence of effectors and of Cl- ions, and the results showed that the allosteric site and the Val 1 alpha residues of conjugated hemoglobin were occupied by dex-BTC. Finally, the fractions obtained after gel filtration exhibited a similar P50 whatever their molecular sizes. So far, all the results obtained are compatible with the use of the conjugate solution as a blood substitute.
Quellec
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Laboratoire de Chimie-Physique Macromoléculaire, URA CNRS 494, ENSIC, Nancy, France.
Léonard
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Grandgeorge
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Dellacherie
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D000495:Allosteric Site; D001802:Blood Substitutes / Q000737:chemistry* / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002712:Chlorides / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008970:Molecular Weight; D010100:Oxygen / Q000378:metabolism; D012996:Solutions
D001802:Blood Substitutes; D002712:Chlorides; D003911:Dextrans; D006454:Hemoglobins; D012996:Solutions; C040953:dextran-hemoglobin complex (deoxygenated); D010100:Oxygen