Synthesis, Physico-Chemical and Biological Properties of Crosslinked Modified Hemoglobin

Abstract

Polymer aspects of polycondensation of pyridoxylated hemoglobin with glutaraldehyde have been considered. On the basis of the investigation of reaction kinetics, the mechanism of chemical crosslinking of hemoglobin molecules into oligohemoglobin is proposed. Owing to the statistical character of the reaction, the resulting macromolecules are polydisperse with respect to the degree of modification of hemoglobin amino groups, and size of oligohemoglobin molecules. The formation of hemoglobin oligomers was studied by varying the following reaction conditions: pH, the components ratio, and their concentrations. It is shown that the net electric charge of the oligohemoglobin molecule depends on the terminating agents. However, these agents have no effect on the electrophoretic mobility of erythrocytes in oligohemoglobin solutions. The efficiency of oxygen transport of these solutions is close to that of human blood erythrocytes. Oligohemoglobin circulation in the blood of animals after intravenous infusion leads to rapid removal of low molecular weight fractions from blood and to the accumulation of high molecular weight fractions in plasma. The period of half-release of oligohemoglobin from the organism is 14-16 h.

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“…Nevertheless, the site where the reaction usually seems to take place is the ε-amino group of the lysine residues and the N-terminal amino groups, where Schiff bases form. It is also possible for glutaraldehyde to cross-link hemoglobin not by Schiff base, but by aldol condensation between glutaraldehyde derivatives bonded to different hemoglobin molecules (64). Glutaraldehyde exerts non-specific binding: it can bind with any of the 44 lysine residues on the four terminal valines on the hemoglobin molecule.…”